MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Leukemia Research' source. Fri, 19 Mar 2010 15:32:28 +0100 http://www.medworm.com/index.php?rid=3296132&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004962%2Fabstract%3Frss%3Dyes Bortezomib (Bercade®) is a proteasome inhibitor, that inhibits the ubiquitin pathway to enter clinical studies . This pathway controls the activation of nuclear factor-kappa B (NF-κB; a major transcription factor) by regulating degradation of the NF-κB inhibitor (I-κB). In cancer, dysregulation of this catalytic process may contribute to tumor progression, drug resistance, and altered immune surveillance. Thus, any inhibition of the proteasome system creates an imbalance of various regulatory proteins, triggering cell cycle arrest in the G1/S and G2/M phases of the cell cycle and in the apoptotic pathways within the cell. The anti-tumor effects of bortezomib are a result of cell cycle arrest and apoptosis or autophagy, resulting from the effects of proteasome inhibition . The underlyin... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296132 Tue, 23 Feb 2010 14:33:41 +0100 3296132 http://www.medworm.com/index.php?rid=3296131&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004901%2Fabstract%3Frss%3Dyes We report a patient with MDS whose pancytopenia was exacerbated by a concurrent littoral cell angioma (LCA), a rare primary vascular tumor arising from the littoral cells of the spleen , and whose blood counts improved substantially following laparoscopic splenectomy. We also review previously published LCA cases, including previous reports of association with hematopoietic stem cell disorders. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296131 Tue, 23 Feb 2010 14:33:41 +0100 3296131 http://www.medworm.com/index.php?rid=3296130&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005141%2Fabstract%3Frss%3Dyes We report the very rare case of CLL diagnosis in a patient suffering from epigastralgia due to peritoneal infiltration. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296130 Tue, 23 Feb 2010 14:33:41 +0100 3296130 http://www.medworm.com/index.php?rid=3296129&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004822%2Fabstract%3Frss%3Dyes Isolated extramedullary relapse (EMR) of chronic myelogenous leukemia (CML) after bone marrow transplantation (BMT) is rare, seen in only 0.21% of cases . EMR in the central nervous system (CNS) is a rare event, and when seen is more commonly associated with lymphoblastic cells . Only two cases of CNS myeloblastic relapse have been reported previously . To our knowledge, isolated CNS myeloid blastic crisis after allogenic BMT for CML has previously not been reported. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296129 Tue, 23 Feb 2010 14:33:41 +0100 3296129 http://www.medworm.com/index.php?rid=3296128&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004871%2Fabstract%3Frss%3Dyes Therapeutic outcome of chronic myelogenous leukemia (CML) in advanced phases and of Philadelphia chromosome-positive (Ph+) acute leukemias remains dismal, even with tyrosine kinase inhibitors (TKIs) against Bcr-Abl or hematopoietic stem cell transplantation (HSCT) with maximally myeloablative conditioning (MAST). Especially, because patients over 55 years old are not eligible for MAST, the establishment of a treatment strategy for elderly patients with acute/advanced Ph+ leukemias has long been anticipated. We here present our experience with the use of fludarabine (Flu)/busulfan (Bu) 16 conditioning regimen (FB16) and dasatinib maintenance therapy following allogenic bone marrow transplantation (BMT) for two elderly patients with Ph+ acute/advanced leukemia. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296128 Tue, 23 Feb 2010 14:33:41 +0100 3296128 http://www.medworm.com/index.php?rid=3296127&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900513X%2Fabstract%3Frss%3Dyes Primary non-Hodgkin's lymphoma (NHL) of the genital tract is extremely rare (0.5%) and mostly originates from the ovary . The cervix lymphoma is 0.008% of the all cervix tumors and 2% of the all extranodal lymphomas in the females . The most common histological type is diffused large B cell lymphoma (DLBCL) . Primary cervical carcinoma, sarcoma or benign inflammatory conditions are kept in mind in differential diagnosis . Histopathological and immunohistochemical examinations of cervix biopsy specimen are required for definitive diagnosis . In staging, computerized tomography (CT) of the pelvis, abdomen and thorax or position emission tomography (PET–CT) can be used. There is not any established treatment protocol for primary cervix lymphoma (PCL) due to rarity of disease. Radiotherapy (... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296127 Tue, 23 Feb 2010 14:33:40 +0100 3296127 http://www.medworm.com/index.php?rid=3296126&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005128%2Fabstract%3Frss%3Dyes We identified for the first time a new BCR-ABL point mutation in a CML patient that developed disease progression to lymphoid blast crisis. Here, we describe the clinical and molecular features of this imatinib-resistant CML patient. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296126 Tue, 23 Feb 2010 14:33:40 +0100 3296126 http://www.medworm.com/index.php?rid=3296125&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005013%2Fabstract%3Frss%3Dyes Plasma cell leukemia (PCL) is an aggressive form of plasma cell proliferation which may both manifest as primary neoplasm (pPCL), or represent the evolution of a pre-existing multiple myeloma (MM), namely secondary plasma cell leukemia (sPCL), which is characterized by a very short median survival, ranging from 1.3 to 2 months . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296125 Tue, 23 Feb 2010 14:33:40 +0100 3296125 http://www.medworm.com/index.php?rid=3296124&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005104%2Fabstract%3Frss%3Dyes We present the case of a primary systemic AL amyloidosis with hepatic, cervical, retroperitoneal, axillary and inguinal lymphnode localizations, unresponsive to medical therapy and treated with a surgical approach followed by autologous bone marrow transplantation. We review the pertinent literature with exclusive attention to the otorhinolaryngologic aspect. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296124 Tue, 23 Feb 2010 14:33:40 +0100 3296124 http://www.medworm.com/index.php?rid=3296123&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004895%2Fabstract%3Frss%3Dyes Abstract: Medullar cord compression secondary to osseous plasmacytomas affecting the vertebrae is an oncological emergency. A 75-year-old woman with recurrent osseous plasmacytomas and thoracic spinal cord compression, previously treated with radiotherapy, was successfully treated with bortezomib and dexamethasone. Three years later, when the plasmacytoma and spinal cord compression relapsed, she was retreated with the same therapeutic scheme, achieving a new complete clinical remission. This is the first reported case of an excellent response to the combination of bortezomib and dexamethasone for spinal cord compression due to osseous plasmacytoma. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296123 Tue, 23 Feb 2010 14:33:40 +0100 3296123 http://www.medworm.com/index.php?rid=3296122&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004858%2Fabstract%3Frss%3Dyes We report here two new cases of JAK2V617F mutation discovered in Ph+ CML patients under imatinib treatment and compare our findings with those of similar reports. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296122 Tue, 23 Feb 2010 14:33:40 +0100 3296122 http://www.medworm.com/index.php?rid=3296121&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900469X%2Fabstract%3Frss%3Dyes We describe a CML patient in chronic phase with F317L mutation who achieved and maintained a complete cytogenetic and a major molecular response on dasatinib treatment. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296121 Tue, 23 Feb 2010 14:33:40 +0100 3296121 http://www.medworm.com/index.php?rid=3296120&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004755%2Fabstract%3Frss%3Dyes A 39-year-old woman presented a history of relapsed acute myeloid leukemia (AML) which allows the discussion of many aspects of clinical and biological features of AML. The initial diagnosis of acute leukemia was made in June 1993. At that time, the myelogram showed 98% undifferentiated peroxidase negative leukemic blasts cells. No tumoral syndrome was found at physical examination. Flow cytometry analysis of leukemic cells revealed an undifferentiated phenotype HLADR+CD7+CD38+ and negative for CD34, CD13, CD33, cMPO−, T and B cell markers. She was classified as AML0 according to the FAB classification which was the one used at this time. Cytogenetic analysis revealed a chromosomal translocation t(10,11) (p12;q21) associated with a trisomy 4. The patient obtained a complete remission af... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296120 Tue, 23 Feb 2010 14:33:40 +0100 3296120 http://www.medworm.com/index.php?rid=3296119&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004846%2Fabstract%3Frss%3Dyes We report a case of a patient with myelodysplastic syndrome (MDS) who developed PNH following therapy with alemtuzumab and whose course was complicated by multiple recurrences of cerebral thrombosis despite anticoagulation. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296119 Tue, 23 Feb 2010 14:33:39 +0100 3296119 http://www.medworm.com/index.php?rid=3296118&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004834%2Fabstract%3Frss%3Dyes I read with great interest the Open Forum published by Domenico Ribatti from Italy. He excellently presented the data about the lymphangiogenesis in tumor progression and cross-talk between VEGF-A and VEGF-C . Ribatti emphasized the anti-angiogenic strategies about the acute leukemias, myelodysplastic syndrome and multiple myeloma but not in lymphomas. Although in limited number, there are papers about lymphangiogenesis and angiogenesis in lymphomas . The largest series about VEGF-C expression in lymphomas was published by our group. Firstly we studied VEGF-C/VEGF-A expressions in 177 cases with lymphoma and then re-evaluated 88 cases with diffuse large B cell lymphoma subset . We found VEGF-C and VEGF-A expression in one third and two thirds of the cases, respectively and also found a goo... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296118 Tue, 23 Feb 2010 14:33:39 +0100 3296118 http://www.medworm.com/index.php?rid=3296117&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005074%2Fabstract%3Frss%3Dyes The authors regret that in the above-published paper the first word of the title was represented incorrectly. It is now represented correctly above. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296117 Tue, 23 Feb 2010 14:33:39 +0100 3296117 http://www.medworm.com/index.php?rid=3296116&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003592%2Fabstract%3Frss%3Dyes Non-Hodgkin's lymphoma (NHL) incidence has rapidly increased since the 1970s. Incidence rates increased proportionally more for extranodal NHL than for nodal NHL . Primary NHL of the thyroid (PNHLT) is an uncommon diagnosis, accounting for 5% of all thyroid malignancies and 2% of primitive extranodal lymphomas, with an incidence of 0.5 per 100,000 population . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296116 Tue, 23 Feb 2010 14:33:39 +0100 3296116 http://www.medworm.com/index.php?rid=3296115&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004779%2Fabstract%3Frss%3Dyes Abstract: Increased BMI has been correlated to an increased incidence of APL, but not to the occurrence of differentiation syndrome (DS) in APL. We consecutively treated 39 APL patients with ATRA and idarubicin (according to PETHEMA regimen). Median age was 26 years. Forty-one percent patients were classified as intermediate risk, and 59% as high risk according to Sanz's score. Thirty-three patients (85%) reached CR. Eleven of the 36 patients evaluable for DS (30.5%) developed this syndrome (severe in 7 cases, moderate in 4, and fatal in 3 cases) within a median of 12 days (range 3–23) of ATRA onset. Six of the 9 (66.6%) patients with BMI≥30 developed DS vs. 5 of 27 (18.5%) with BMI1.4mg/dl (p=0.009). In multivariate analysis, BMI≥30 remained an independent predictor of DS in additio... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296115 Tue, 23 Feb 2010 14:33:39 +0100 3296115 http://www.medworm.com/index.php?rid=3296114&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004688%2Fabstract%3Frss%3Dyes Chronic myeloid leukemia (CML) is usually an insidious disease and the median age at diagnosis is stated in Hematology text books to be around 50 years. In the past, patients seek medical attention as a consequence of symptoms of vigorous hematopoiesis (fever, sweats, bone pain, weight loss, and fatigue) or signs of extramedullary hematopoiesis (splenomegaly and left upper quadrant discomfort). However, current medical practice and the periodic routine medical evaluation resulted in shifts in clinicohematologic picture and it is becoming more common for patients to be diagnosed before the development of symptoms . Considering such shift, it was expected that average age at diagnosis could be younger. However, the age was significantly lower in interferon studies than in recent imatinib mes... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296114 Tue, 23 Feb 2010 14:33:39 +0100 3296114 http://www.medworm.com/index.php?rid=3296113&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003907%2Fabstract%3Frss%3Dyes Abstract: We have previously shown that inhibition of translation initiation, using the small molecule inhibitor silvestrol, induces apoptosis in a pre-clinical murine lymphoma model when combined with daunorubicin. Silvestrol blocks ribosome recruitment by targeting the RNA helicase, eIF4A, which is required for this process. Here we investigate the sensitivity of acute myelogenous leukemia (AML) cell lines to protein synthesis inhibition in combination with the standard cytotoxic agents daunorubicin, etoposide, and cytarabine. Silvestrol shows synergy with standard-of-care agents in AML cell lines and synergizes with ABT-737, a small molecule inhibitor of Bcl-XL and Bcl-2. The in vitro synergy between silvestrol and the cytotoxic drugs used in AML therapy provides a basis for in vivo eva... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296113 Tue, 23 Feb 2010 14:33:39 +0100 3296113 http://www.medworm.com/index.php?rid=3296112&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003452%2Fabstract%3Frss%3Dyes Abstract: Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and are used in the therapy of lymphoid malignancies. SLA (Src-like-adaptor), an inhibitor of T- and B-cell receptor signaling, is a promising candidate derived from expression profiling analyses in children with acute lymphoblastic leukemia (ALL). Over-expression and knock-down experiments in ALL in vitro model revealed that transgenic SLA alone had no effect on survival or cell cycle progression, nor did it affect sensitivity to, or kinetics of, GC-induced apoptosis. Although SLA is a prominent GC response gene, it does not seem to contribute to the anti-leukemic effects of GC. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296112 Tue, 23 Feb 2010 14:33:38 +0100 3296112 http://www.medworm.com/index.php?rid=3296111&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002975%2Fabstract%3Frss%3Dyes In conclusion, we identified multiple mechanisms which activate LYL1 in leukemic cells, including structural genomic alterations, namely microdeletion or amplification, together with the involvement of prominent oncogenic transcription factors. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296111 Tue, 23 Feb 2010 14:33:38 +0100 3296111 http://www.medworm.com/index.php?rid=3296110&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004998%2Fabstract%3Frss%3Dyes Abstract: All-trans retinoic acid (ATRA) affects on the function of antigen presenting cells with somewhat controversies. We investigated the effects of ATRA on differentiation, maturation and function of human monocyte-derived dendritic cells (DCs). Low dose (10−14M) or high dose (10−6M) of ATRA was added either when monocytes were differentiated into immature DCs (imDCs) or mature DCs (mDCs) were induced. Apoptotic cell populations were dramatically increased in imDCs or mDCs with increasing concentration of ATRA. The productions of IL-12p40 and IL-12p70 were significantly suppressed in imDCs or mDCs induced by the addition of ATRA in the dose-dependent manner, whereas IL-10 was increased. DCs cultured with ATRA induced the differentiation of naïve T cells towards a helper T cell ty... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296110 Tue, 23 Feb 2010 14:33:38 +0100 3296110 http://www.medworm.com/index.php?rid=3296109&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005050%2Fabstract%3Frss%3Dyes Abstract: Stromal cells from pediatric myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) associated with MDS (MDS-AML) present high expression of leukemia inhibitor factor (LIF). We demonstrated using mitogen-activated protein kinase (MAPK) inhibitors that in stromal cells from pediatric MDS and MDS-AML, p38MAPK was critical in serum-induced secretion of LIF. The serum induction of phosphorylated p38MAPK form was observed only in stromal cells from healthy children, whereas in MDS and MDS-AML basal levels were maintained suggesting constitutive p38MAPK activation. Our study suggested the possible importance in pediatric MDS of p38MAPK signaling pathway which may be a future therapeutic target. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296109 Tue, 23 Feb 2010 14:33:38 +0100 3296109 http://www.medworm.com/index.php?rid=3296108&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004809%2Fabstract%3Frss%3Dyes In this study, we investigated the induction of apoptosis by proteasome inhibitors in several human acute myeloid leukemia (AML) cell lines and in primary cells from patients. We demonstrate that these drugs induce a high level of apoptosis in the KG1a cell line, in which the therapeutic drug daunorubicin is poorly active, compared to other AML cell lines. In parallel, we found that significantly different levels of apoptosis were induced in primary cells from patients depending on the FAB-based differentiation status of these cells. Moreover, the level of 20S proteasome in KG1a cells was also high compared to other AML cell lines, suggesting a relationship between the high sensitivity to proteasome inhibitors and an elevated amount of 20S proteasome. In good accordance, we identified two ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296108 Tue, 23 Feb 2010 14:33:38 +0100 3296108 http://www.medworm.com/index.php?rid=3296107&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900410X%2Fabstract%3Frss%3Dyes Abstract: Childhood acute lymphoblastic leukemia patients (n=310) were analyzed for four SNPs in the NR3C1 gene. Polymorphisms −627A/G, intron 2 +646C/G and 9bT/C were all associated with reduced event-free survival. Haplotypes composed of AGT alleles at these loci and tagged by the intron 2 +646G variant also associated with lower event-free survival (p=0.03). The progressive impact of this haplotype on outcome was seen with two copies associated with reduced overall survival (p=0.05). Quantitative mRNA analysis in lymphoblastoid cell lines showed that carriers of the AGT haplotype had a higher ratio of GR γ/α isoforms (p=0.04), which possibly explains its association with reduced event-free survival and overall survival. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296107 Tue, 23 Feb 2010 14:33:38 +0100 3296107 http://www.medworm.com/index.php?rid=3296106&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003877%2Fabstract%3Frss%3Dyes Abstract: Amonafide-l-malate (amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML. 43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine. 3/17 patients in the monotherapy trial and 10/26 patients in the combination trial achieved a complete remission. Between both trials responses occurred in 9/20 patients with secondary AML. Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296106 Tue, 23 Feb 2010 14:33:38 +0100 3296106 http://www.medworm.com/index.php?rid=3296105&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003385%2Fabstract%3Frss%3Dyes Abstract: T-cell acute lymphoblastic leukemia (T-ALL) may affect children in very early age. However, the critical events leading to this brief latency is still unclear. We used standard methods to explore NOTCH1 mutations and other specific molecular markers in 15 early childhood T-ALL cases. Most of them consisted of immature differentiation subtype. Despite being found in a lower frequency than that described for overall pediatric T-ALL, NOTCH1 alterations were the most frequent ones. Other alterations included MLL+ (n=4), SIL-TAL1+ (n=3), FLT3 mutation (n=1) and HOX11L2+ (n=1). Our results suggest that NOTCH1 and MLL abnormalities are primary leukemogenic hits in early T-ALL. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296105 Tue, 23 Feb 2010 14:33:37 +0100 3296105 http://www.medworm.com/index.php?rid=3296104&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900383X%2Fabstract%3Frss%3Dyes Abstract: CD30-positive anaplastic large cell lymphoma (ALCL) is a distinctive malignant large cell lymphoma of T-cell lineage, often presenting in lymph node or extranodal sites. ALCL cases with extensive bone marrow and peripheral blood involvement manifested as “leukemic phase” are extremely rare and the most of those cases reported are anaplastic large cell lymphoma kinase (ALK) positive ALCL in childhood population. Here we report four adult cases of ALK-negative ALCL with extensive bone marrow and peripheral blood involvement manifested as “leukemic phase”. Circulating large lymphoma cells varied from 20 to 80% in peripheral blood and bone marrow biopsy showed various nodular or interstitial infiltrates. By reviewing the clinicopathologic data of previously reported ALCL case... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296104 Tue, 23 Feb 2010 14:33:37 +0100 3296104 http://www.medworm.com/index.php?rid=3296103&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003658%2Fabstract%3Frss%3Dyes In conclusion, incidence, severity and outcome of bortezomib-related PN are similar in untreated and pre-treated MM patients except for neuropathic pain which has lower incidence and shorter duration in untreated patients with less frequent need for bortezomib discontinuation. Age emerges as the most relevant risk factor for peripheral neuropathy, with a risk increase for PN of 6% per year of age. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296103 Tue, 23 Feb 2010 14:33:37 +0100 3296103 http://www.medworm.com/index.php?rid=3296102&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003890%2Fabstract%3Frss%3Dyes Abstract: Altered sialylation occurs in essentially all types of human and experimental cancers. Although, aberrant sialylation is believed to mainly due to altered sialyltransferase (ST) level, so far, expression pattern of different STs in acute lymphoblastic leukemia has never been investigated. Accordingly, the aim of our study was to monitor the changes in mRNA expression of ST6Gal I, ST3Gal V and ST8Sia I in patients by real-time PCR, which may provide prognostic information useful in defining appropriate therapeutic options. Our data demonstrated that ST6Gal I and ST3Gal V mRNA were up-regulated in lymphoblasts whereas its presence was negligible in non-malignant donors. In contrast, ST8SiaI was downregulated in patients. The extents of linkage-specific sialylation of glycoconjugate... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296102 Tue, 23 Feb 2010 14:33:37 +0100 3296102 http://www.medworm.com/index.php?rid=3296101&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900352X%2Fabstract%3Frss%3Dyes Abstract: Purpose: To investigate clinical characteristic and prognostic factors for chronic myelomonocytic leukemia (CMML).Methods: A retrospective cohort study was used in the research. We investigated clinical and laboratory characteristics of CMML patients and survival status. Patients were followed up regularly through out the course of the research.Results: Forty-one cases were diagnosed as CMML, including 27 male and 14 female patients. Median WBC was 13.7×109/L. Five patients had leukocytopenia (1.92–3.46×109/L). Median monocyte count in the peripheral blood was 2.13×109/L. All patients presented with bone marrow dysplasia, and most showed hyperplasia, except 3 cases. Abnormal chromosome was detected in 34% cases. Median survival time for CMML-1 and CMML-2 was 20 and 12 months... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296101 Tue, 23 Feb 2010 14:33:37 +0100 3296101 http://www.medworm.com/index.php?rid=3296100&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900349X%2Fabstract%3Frss%3Dyes This study suggests that nucleotidase expression levels can be used to identify subgroups of WM and SLL patients who will likely respond differently to a 2CdA-based therapy. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296100 Tue, 23 Feb 2010 14:33:37 +0100 3296100 http://www.medworm.com/index.php?rid=3296099&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004287%2Fabstract%3Frss%3Dyes Abstract: Cytogenetic aberrations identified by metaphase cytogenetics (MC) have important diagnostic, prognostic and therapeutic roles in myelodysplastic syndromes (MDS). Fluorescence in situ hybridization (FISH) complements MC by the ability to evaluate large numbers of both interphase and metaphase nuclei. However, clinically practical FISH strategies are limited to detection of known lesions. Single nucleotide polymorphism array (SNP-A)-based karyotyping can reveal unbalanced defects with superior resolution over MC and FISH and identify segmental uniparental disomy (UPD) undetectable by either method. Using a standardized approach, we focused our investigation on detection of −5/del(5q), −7/del(7q), trisomy 8 and del(20q) in patients with MDS (N=52), MDS/myeloproliferative overlap... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296099 Tue, 23 Feb 2010 14:33:36 +0100 3296099 http://www.medworm.com/index.php?rid=3296098&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004664%2Fabstract%3Frss%3Dyes We present a cohort of 22 patients with type 2 dendritic cell (DC2) acute leukemia (or blastic plasmacytoid dendritic cell neoplasm-BPDCN, as it has been recently named), diagnosed in Greece over the past 12-year period, according to the main clinical and immunophenotypic features of this entity. Four additional cases are discussed, classified as leukemia of ambiguous lineage (LAL), because of the simultaneous detection of a CD56 negative DC2 population and of a second myeloid precursor cell population. The morphological features and cytogenetic findings of the typical BPDCN cases were similar to those previously described. Acute lymphoblastic leukemia-type chemotherapeutic regimens were more efficient in controlling the disease. Immunophenotyping of typical BPDCN cases revealed CD4+, CD56... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296098 Tue, 23 Feb 2010 14:33:36 +0100 3296098 http://www.medworm.com/index.php?rid=3296097&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004937%2Fabstract%3Frss%3Dyes Abstract: CD9 has been shown to be differentially expressed in childhood TEL/AML1-positive acute lymphoblastic leukemia (ALL). We confirmed this finding in large Affymetrix data sets and in 80 new cases at both RNA and protein levels. Moreover, we showed that mean fluorescence intensity of CD9 by flow cytometry can distinguish TEL/AML1-positive ALL from other BCP-ALL. Using ROC analysis, the most efficient model for predicting TEL/AML1-positive ALL combined CD9 (mean fluorescence intensity ≤20) and CD10 values (positive cells >40%). Finally, we propose a faster procedure for optimizing the diagnosis of childhood BCP-ALL subgroups. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296097 Tue, 23 Feb 2010 14:33:36 +0100 3296097 http://www.medworm.com/index.php?rid=3296096&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900472X%2Fabstract%3Frss%3Dyes Abstract: The Ikaros (Ikzf1) gene, encoding a transcription regulator, is a major tumor suppressor in B-cell acute lymphoblastic leukemia (B-ALL). In the mouse, however, loss of Ikaros is primarily associated with T-ALL development. Whether Ikaros is also implicated in human T-ALL remains unclear. We studied Ikaros in 25 human T-ALL samples from diverse molecular subtypes at the mRNA, protein, sequence and genomic copy number level. We found that Ikaros was abnormal in only one sample: one allele was lost by genomic deletion, while proteins generated from the remaining allele were delocalized and concentrated at a single cytoplasmic structure. Thus, inactivation of Ikaros by deletion or mutation is rare in human T-ALL. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296096 Tue, 23 Feb 2010 14:33:36 +0100 3296096 http://www.medworm.com/index.php?rid=3296095&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004731%2Fabstract%3Frss%3Dyes Abstract: Cytogenetic analysis provides important diagnostic and prognostic information for patients with myelodysplastic syndromes (MDS). Prior studies, mostly comprised of small sample sizes, have reported conflicting results while evaluating the usefulness of FISH in addition to G-band karyotyping in MDS. In the current study, the utility of performing a tailored FISH panel, in addition to G-band karyotyping was evaluated in a series of 110 MDS patients diagnosed at our institute. Using our FISH panel, clonal cytogenetic abnormalities were detected in 3/8 (38%) of MDS cases with karyotype failure and in 5/54 (9%) cases with normal G-band karyotypes, all the latter had intermediate or high grade MDS. Of the cases with abnormal G-band karyotypes, 6/48 (13%) showed discrepancies between FI... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296095 Tue, 23 Feb 2010 14:33:36 +0100 3296095 http://www.medworm.com/index.php?rid=3296094&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005025%2Fabstract%3Frss%3Dyes The advent of molecular medicine has allowed physicians and scientists to decipher some of nature's mysteries. Few stories are more exhilarating than that of the successes in pediatric acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML). Indeed, children with ALL are now curable without the need for cranial radiation and imatinib mesylate has changed the landscape of CML therapy . Despite these advances disease recurrence and adverse late effects continue to dampen our celebrations. Enticing dormant cancer stem cells to undergo mitosis and offering risk-directed therapy are current endeavors aimed to overcome these obstacles. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296094 Tue, 23 Feb 2010 14:33:36 +0100 3296094 http://www.medworm.com/index.php?rid=3296093&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005037%2Fabstract%3Frss%3Dyes The Ikaros gene encodes a DNA-binding protein that belongs to the C2H2 zinc finger gene family . Early biological experiments using mutant mouse models demonstrated that a lack of Ikaros expression in mice results in the absence of B, NK and dendritic cells, with a decreased number of T cells . These experiments established Ikaros as a master-regulator of lymphoid development. Subsequent analysis of Ikaros-deficient mice revealed that the absence of Ikaros expression, or the presence of dominant-negative Ikaros mutants, leads to the development of T cell leukemia in mice. This suggested that Ikaros acts as a tumor suppressor . The identification of Ikaros as a master-regulator of lymphoid development and a tumor suppressor provided a novel model to study the development of leukemia, as wel... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296093 Tue, 23 Feb 2010 14:33:36 +0100 3296093 http://www.medworm.com/index.php?rid=3296092&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005049%2Fabstract%3Frss%3Dyes Myelodysplastic syndrome (MDS) represents a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis. Despite peripheral cytopenias, bone marrow is usually hypercellular with morphological dysplasia, increased apoptosis, genetic instability and an additional risk to evolve to acute leukemia in around 30% of the cases . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296092 Tue, 23 Feb 2010 14:33:35 +0100 3296092 http://www.medworm.com/index.php?rid=3296091&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004810%2Fabstract%3Frss%3Dyes Bortezomib is an inhibitor of the proteasome that represents one of the most intriguing drugs that has been recently introduced in clinical practice. Its use in the treatment of multiple myeloma has increased percentage of complete response and, most remarkably, it has improved disease free and overall survival, thus playing a pivotal role in the treatment of this disease . The activity of Bortezomib is not limited to myeloma since it has recently received the approval for treatment of relapsed mantle cell lymphoma patients and several clinical trials are currently conducted in the United States and around the world on different malignancies (www.clinicaltrials.gov). Notwithstanding the clinical successes, there is a gap between what we know on the in vitro activity of this drug and its cl... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296091 Tue, 23 Feb 2010 14:33:35 +0100 3296091 http://www.medworm.com/index.php?rid=3296090&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004718%2Fabstract%3Frss%3Dyes Myelodysplasia is a Greek word meaning “morphological abnormality of the marrow” and may be seen in different disorders including autoimmune/infective/chronic diseases, megaloblastic anemias, and toxic susbstance exposure. For this reason myelodysplasia requires a long list of differential diagnoses. The myelodysplastic syndrome (MDS) diagnosis is based on the exclusion of other disorders and is characterized by ineffective hematopoiesis, quantitative/qualitative cellular defects and moderate risk of leukemic transformation. Abnormal differentiation/maturation of myeloid cells, bone marrow failure and genetic instability are the hallmarks of this heterogenous entity. In clinical practice the first step is to differentiate myelodysplasia from MDS. Diagnosis of MDS requires a team of exp... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296090 Tue, 23 Feb 2010 14:33:35 +0100 3296090 http://www.medworm.com/index.php?rid=3296089&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212610000639%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3296089 Tue, 23 Feb 2010 14:33:35 +0100 3296089 http://www.medworm.com/index.php?rid=3264441&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900280X%2Fabstract%3Frss%3Dyes Abstract: Acute lymphoblastic leukemia (ALL) with chromosome aberration t(8;14)(q11.2;q32) mostly affects patients younger than 20 years old. One third of patients with this translocation have been reported to have Down syndrome. This translocation has been reported rarely in patients over the age of 50. Here we report a 71-year-old male ALL patient who carried t(8;14)(q11.2;q32). Fluorescence in situ hybridization (FISH) analysis revealed the involvement of CCAAT enhancer-binding protein delta (CEBPD) gene on chromosome 8, and IgH gene on chromosome 14. This case provides a new aspect for considering this clinical entity. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264441 Fri, 12 Feb 2010 14:22:44 +0100 3264441 http://www.medworm.com/index.php?rid=3264440&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003725%2Fabstract%3Frss%3Dyes We report the case of an 80-year-old patient with AML-M1 who was diagnosed with LCH after biopsy of a lymph node that appeared during induction chemotherapy. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264440 Fri, 12 Feb 2010 14:22:44 +0100 3264440 http://www.medworm.com/index.php?rid=3264439&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003932%2Fabstract%3Frss%3Dyes Abstract: We assessed concentrations of arsenic trioxide (As2O3) and its metabolites in the plasma and cerebrospinal fluid in acute promyelocytic leukemia patients who achieved complete remission with intravenous As2O3. Arsenic trioxide exists as high molecular mass proteins and low molecular mass proteins in the plasma, and metabolites seem to be able to penetrate blood–brain barrier. Methylarsonic acid (MA) in the cerebrospinal fluid is stably detected and its level was higher than that in plasma after As2O3 treatment. Trivalent arsenic (ASIII) and dimethylarsinic acid (DMA) became detectable after As2O3 infusion, though the levels of arsenic metabolites in the cerebrospinal fluid was lower than plasma levels. Results suggest that a combinatory treatment of As2O3 with other chemotherap... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264439 Fri, 12 Feb 2010 14:22:44 +0100 3264439 http://www.medworm.com/index.php?rid=3264438&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004433%2Fabstract%3Frss%3Dyes Abstract: Tissue inhibitor of metalloproteinase-1 (TIMP-1) was evaluated in the pre-treatment serum of 55 newly diagnosed patients with symptomatic myeloma. TIMP-1 was elevated in 47% of patients and correlated with lytic bone disease and increased bone resorption. Importantly, TIMP-1 correlated with ISS stage (p=0.005) and was an independent prognostic covariate for survival [HR: 1.003 (1–1.006), p=0.004] in these patients who were all treated with novel agents (bortezomib and/or IMiDs) during their disease course. Our study provides evidence that pre-treatment serum TIMP-1 is associated with advanced myeloma and suggests the further evaluation of this molecule to better determine its prognostic potential in MM. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264438 Fri, 12 Feb 2010 14:22:44 +0100 3264438 http://www.medworm.com/index.php?rid=3264437&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004445%2Fabstract%3Frss%3Dyes In conclusion, we found an association of low NDRG1 levels with an immature cell phenotype and provide evidence that NDRG1 is functionally involved in neutrophil maturation. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264437 Fri, 12 Feb 2010 14:22:44 +0100 3264437 http://www.medworm.com/index.php?rid=3264436&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003403%2Fabstract%3Frss%3Dyes This study has interviewed 117 patients with haemato-oncological illnesses at two assessment dates. The desired and the (in the follow up) perceived role in the medical decision-making process were documented. The majority (60.2%) desired more a passive role, which is a considerably higher portion than with solid cancer cases. Roughly every second person interviewed (55.7%) was included – mostly passively – in decisions in accordance with his preferences. The results and limits of the study are also discussed. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264436 Fri, 12 Feb 2010 14:22:44 +0100 3264436 http://www.medworm.com/index.php?rid=3264435&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900294X%2Fabstract%3Frss%3Dyes We report three novel mutations in JAK2 exons 12, 19 and 25 in V617F-negative patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. Scanning of JAK2 exons 12–25 and MPL exon 10 revealed the presence of JAK2 alterations in six and MPL W515L/K mutations in five of 34 patients with myeloproliferative disorders. Our results confirm that routine JAK2 analysis should include exon 12 mutations in polycythemia vera patients. MPL gene mutations seem to be associated with thrombocytosis, regardless of the type of myeloproliferative neoplasm. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264435 Fri, 12 Feb 2010 14:22:43 +0100 3264435 http://www.medworm.com/index.php?rid=3264434&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003610%2Fabstract%3Frss%3Dyes Abstract: Interactions between the multi-kinase inhibitor sorafenib and MEK1/2 inhibitors were investigated in DLBCL cells. Sorafenib (3–10μM) triggered apoptosis in multiple GC and ABC lymphoma cells. Unexpectedly, sorafenib did not cause sustained ERK1/2 inactivation, and in SUDHL-6 and -16 cells, triggered ERK1/2 activation. Marginally toxic MEK1/2 inhibitor concentrations (5μM PD184352) abrogated ERK1/2 activation in sorafenib-treated cells and synergistically potentiated apoptosis. MEK1 shRNA transfection also significantly increased sorafenib-mediated lethality. Sorafenib/PD184352 co-administration accelerated Mcl-1 down-regulation without up-regulating BimEL. Finally, ectopic Mcl-1 expression attenuated sorafenib/PD184352-mediated apoptosis. Together, these findings provide a th... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264434 Fri, 12 Feb 2010 14:22:43 +0100 3264434 http://www.medworm.com/index.php?rid=3264433&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002720%2Fabstract%3Frss%3Dyes In this study, we examined whether reactive oxygen species (ROS) were involved in capillary leak phenomenon in RAS, using NB4 cells. When cells were stimulated by phorbol 12-myristate 13-acetate, RA-treated cells with matured myeloperoxidase produced toxic ROS, such as singlet oxygen, hypochlorous acid and hydroxyl radical, and brought about endothelial hyperpermeability. Leukemic cells from a patient also produced toxic ROS. These findings indicated that toxic ROS contribute to the development of capillary leak phenomenon in RAS. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264433 Fri, 12 Feb 2010 14:22:43 +0100 3264433 http://www.medworm.com/index.php?rid=3264432&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004172%2Fabstract%3Frss%3Dyes Abstract: Busulfan (Bu) is a DNA-alkylating drug used in myeloablative pretransplant conditioning therapy for patients with myeloid leukemia (ML). A major obstacle to successful treatment is cellular Bu-resistance. To investigate the possible contribution of DNA hypermethylation to Bu-resistance, we examined the cytotoxic activity of combined 5-aza-2′-deoxycytidine (DAC) and Bu. Exposure of Bu-resistant B5/Bu2506 ML cells to 0.5μM DAC resulted in G2-arrest and apoptosis. The observed G2-arrest was associated with hypomethylation and subsequent expression of epigenetically controlled genes including p16INK4A, activation of the p53 pathway, and phosphorylation of CDC2. The DAC-mediated apoptosis was partly due to hypomethylation and up-regulation of XAF1, which resulted in down-regulation... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264432 Fri, 12 Feb 2010 14:22:43 +0100 3264432 http://www.medworm.com/index.php?rid=3264431&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002793%2Fabstract%3Frss%3Dyes Abstract: Aberrant expression of the TLX1/HOX11 proto-oncogene is associated with a significant subset of T-cell acute lymphoblastic leukemias (T-ALL). Yet the manner in which TLX1 contributes to oncogenesis is not fully understood. Since, typically, interactions of HOX and TALE homeodomain proteins are determinant of HOX function, and HOX/MEIS co-expression has been shown to accelerate some leukemias, we systematically examined whether TLX1 interacts with MEIS and PBX proteins. Here, we report that TLX1 and MEIS proteins both interact and are co-expressed in T-ALL, and suggest that co-operation between TLX1 and MEIS proteins may have a significant role in T-cell leukemogenesis. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264431 Fri, 12 Feb 2010 14:22:43 +0100 3264431 http://www.medworm.com/index.php?rid=3264430&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004639%2Fabstract%3Frss%3Dyes We examined the effect of deguelin, a naturally occurring rotenoid, on HTLV-1-transformed T-cell lines, KUT-1 and MT-2 cells. We found that deguelin suppressed cell proliferation and induced cell death in these cells. Immunoblot analysis showed the inhibition of survivin expression and signal transducers, and activators of transcription (STAT) 3 phosphorylation of both cells. We also observed the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP) in deguelin-treated cells, indicating that deguelin induces caspase-dependent apoptosis in these cells. Furthermore, proteasome inhibitor MG132 prevented the down-regulation of survivin expression and STAT3 dephosphorylation by deguelin, suggesting that the action mechanism of deguelin involves the degradation of survivin and phosphoryla... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264430 Fri, 12 Feb 2010 14:22:43 +0100 3264430 http://www.medworm.com/index.php?rid=3264429&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003476%2Fabstract%3Frss%3Dyes Abstract: Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264429 Fri, 12 Feb 2010 14:22:43 +0100 3264429 http://www.medworm.com/index.php?rid=3264428&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900277X%2Fabstract%3Frss%3Dyes Abstract: To determine the clinical utility of FISH for del(5q) in MDS/AML, we first compared FISH for 5q31 (EGR1) and 5q33 (CSF1R) in 51 myeloid neoplasms containing del(5q) by metaphase cytogenetics. Next, EGR1 FISH was compared to metaphase cytogenetics alone in 269 cases of known or suspected MDS/AML. These studies show that while metaphase cytogenetics alone can detect del(5q) in most cases, FISH is particularly useful in cases with suboptimal growth. EGR1 FISH detects del(5q) in a broad variety of myeloid neoplasms, including at least most cases of 5q− syndrome, while studies for CSF1R add little to the diagnostic yield. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264428 Fri, 12 Feb 2010 14:22:43 +0100 3264428 http://www.medworm.com/index.php?rid=3264427&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002835%2Fabstract%3Frss%3Dyes Abstract: The 309T>G polymorphism in the promoter region of the MDM2 gene, known as SNP309, has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. To investigate this further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated the results with established CLL prognostic factors, time to treatment and overall survival. In this Swedish cohort, no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment. Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet stage, IGHV mutational status and recurrent genomic aberrations. In summary, this study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL. (... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264427 Fri, 12 Feb 2010 14:22:42 +0100 3264427 http://www.medworm.com/index.php?rid=3264426&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002902%2Fabstract%3Frss%3Dyes Abstract: We investigated whether, in myelodysplastic syndromes (MDS), aberrant expression of miR-150/miR-221/miR-222 and their designated target mRNA molecules MYB, p27 and c-KIT may be involved in insufficient haematopoiesis. In a series of MDS (n=52), an aberrant increase of miR-150 was found only in MDS with associated del(5q) (n=9; p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264426 Fri, 12 Feb 2010 14:22:42 +0100 3264426 http://www.medworm.com/index.php?rid=3264425&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004226%2Fabstract%3Frss%3Dyes Abstract: Mismatch repair (MMR) deficiency is a common feature of acute lymphoblastic leukaemia (ALL) cell lines and in some cases is due to the mutations of hMLH1 which affect mRNA splicing. Therefore, we have analysed alternative splicing of hMLH1 in a cohort of children with ALL. We show that alternative splicing of hMLH1 is highly variable in normal and leukaemic cells and can occur by exon skipping or by the use of an alternative splice site, both serving to down-regulate the amount of full-length hMLH1 mRNA/protein produced. Aberrant splicing was found in one child with an aggressive leukaemia in which there was a predominant hMLH1Δ6 form and an associated loss of wild-type hMLH1 protein but this was not accompanied by microsatellite instability. Functional analysis of one of the mo... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264425 Fri, 12 Feb 2010 14:22:42 +0100 3264425 http://www.medworm.com/index.php?rid=3264424&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003191%2Fabstract%3Frss%3Dyes Abstract: Emerging evidence suggests that angiogenic signalling pathways play important role in the patho-biology of chronic lymphocytic leukemia (CLL). Our goal was to investigate: (i) the spontaneous and hypoxia-induced production of pro-angiogenic factors, VEGF and Ang2, by Real-time PCR and ELISA, (ii) the degree of vascularization in CLL-infiltrated bone marrow (BM) compartment by CD34 immunohistochemical staining of microvessels and (iii) the direct angiogenic effect of CLL-derived VEGF and Ang2 by function-blocking experiments in Matrigel assays. The results demonstrated that CLL cells spontaneously express both VEGF and Ang2 and are able to secrete these factors in surrounding microenvironment. Full-length Ang2 mRNA and truncated form Ang2443 were detectable. Moreover, CLL cells we... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264424 Fri, 12 Feb 2010 14:22:42 +0100 3264424 http://www.medworm.com/index.php?rid=3264423&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002823%2Fabstract%3Frss%3Dyes Abstract: The monoclonal antibody Rituximab is useful for treatment of patients with B-cell non-Hodgkin's lymphoma. We phenotypically analyzed reconstitution of peripheral B cells in a male patient with follicular lymphoma following their depletion with Rituximab. CD19+ and CD20+ B cell counts in peripheral blood decreased rapidly following Rituximab treatment. Six months after the end of treatment, a few CD19+ B cells were detected in peripheral blood. These cells had a naive B cell phenotype (IgD+, CD27−) and they expressed high levels of CD38 and CD24, which show that the B cell pool was repopulated mainly with immature, naive B cells. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264423 Fri, 12 Feb 2010 14:22:42 +0100 3264423 http://www.medworm.com/index.php?rid=3264422&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003828%2Fabstract%3Frss%3Dyes Abstract: Lipoprotein lipase (LPL) expression has been shown to correlate with IGHV mutational status and to predict outcome in chronic lymphocytic leukemia (CLL). We here investigated the prognostic impact of LPL expression in relation to other prognostic markers including IGHV3-21 usage in 140 CLL patients. Additionally, we studied the catalytic activity of LPL in CLL cells. A significant difference in LPL mRNA expression was detected in IGHV unmutated compared to mutated CLL patients (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264422 Fri, 12 Feb 2010 14:22:42 +0100 3264422 http://www.medworm.com/index.php?rid=3264421&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004275%2Fabstract%3Frss%3Dyes Abstract: We analyzed the prognostic factors from 259 cases of febrile neutropenia occurring in 137 patients with hematologic disease. Based on multivariate analysis, significant prognostic factors are recovery of neutropenia, respiratory infection, baseline serum albumin, baseline bicarbonate, baseline CRP, and CRP on the fifth day after antibiotic treatment. From these variables, we derived a predictive model for the prognosis of febrile neutropenia using baseline serum albumin, bicarbonate, and CRP, which could be easily checked before chemotherapy. Further studies in prospective setting are needed for the validation of this model. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264421 Fri, 12 Feb 2010 14:22:42 +0100 3264421 http://www.medworm.com/index.php?rid=3264420&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002677%2Fabstract%3Frss%3Dyes Abstract: The Aiolos transcription factor plays a crucial role in the control of lymphocyte differentiation and proliferation. The expression of Aiolos isoform has been studied in lymphoid pathologies but nothing is known about its expression in unaffected human hematopoietic subpopulations. In this manuscript we show for the first time the differential Aiolos expression at the RNA and protein level in hematopoietic cell subpopulations. B cells express higher levels of Aiolos than NK and T cells while monocytes express almost undetectable levels of Aiolos. Moreover, human CD34 (+) progenitors do not express Aiolos. We did not observe significant difference when comparing naive to memory T and B cells, but we observed an important difference between Bright and Dim NK cells. Furthermore, we ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264420 Fri, 12 Feb 2010 14:22:41 +0100 3264420 http://www.medworm.com/index.php?rid=3264419&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003555%2Fabstract%3Frss%3Dyes Abstract: Randomized trials demonstrated the superiority of chemoimmunotherapy over chemotherapy in the frontline treatment of CLL. Based on favorable experience with the addition of mitoxantrone (M) to fludarabine (F) plus cyclophosphamide (C), we designed a pilot study testing the combination of FCM plus rituximab (R). Thirty patients with previously untreated, symptomatic CLL, (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264419 Fri, 12 Feb 2010 14:22:41 +0100 3264419 http://www.medworm.com/index.php?rid=3264418&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003488%2Fabstract%3Frss%3Dyes Abstract: To study genetic epidemiology of childhood acute lymphoblastic leukemia (ALL) in the Chinese and Malays, we investigated 10 polymorphisms encoding carcinogen- or folate-metabolism and transport. Sex-adjusted analysis showed NQO1 609CT significantly protects against ALL, whilst MTHFR 677CT confers marginal protection. Interestingly, we observed that NQO1 609CT and MTHFR 1298 C-allele have greater genetic impact in boys than in girls. The combination of SLC19A1 80GA heterozygosity and 3′-TYMS −6bp/−6bp homozygous deletion is associated with reduced ALL risk in Malay boys. Our study has suggested the importance of gender and race in modulating ALL susceptibility via the folate metabolic pathway. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264418 Fri, 12 Feb 2010 14:22:41 +0100 3264418 http://www.medworm.com/index.php?rid=3264417&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003841%2Fabstract%3Frss%3Dyes Despite improvements in the therapy of patients with chronic lymphocytic leukemia (CLL), the vast majority of patients cannot be cured with current treatment strategies. Purine nucleoside analog (PNA) therapy has had an important impact on the treatment of CLL in the last 20 years. The most widely used agent from this group of antileukemic drugs, fludarabine (FA), induces response in approximately 70% of previously untreated patients, with a minority achieving a complete response (CR). The advantage of PNA over alkylating agent, chlorambucil as the first-line therapy was confirmed in randomized clinical trials . PNA combined with cyclophosphamide (CY) represents a significant advantage over a single agent in terms of an overall response (OR), CR and progression free survival (PFS) . Howeve... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264417 Fri, 12 Feb 2010 14:22:41 +0100 3264417 http://www.medworm.com/index.php?rid=3264416&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003853%2Fabstract%3Frss%3Dyes Childhood acute lymphoblastic leukemia (ALL) is a multifactorial disease resulting from complex interplay between inherited genetic background and specific environmental exposure . As in other multifactorial diseases, it is suggested that common polymorphisms might contribute to the susceptibility to the development of ALL . Because until now no hypothesis free genome wide association study has been carried out in ALL, candidate gene association studies offer a relative simple and reasonable way to reveal the genetic background of the disease. In ALL candidate genes might be genes coding for proteins involved in metabolism or transportation of environmental carcinogens and folates or those that help to protect the integrity of the genome . In the last decades it has been showed that reveal... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264416 Fri, 12 Feb 2010 14:22:41 +0100 3264416 http://www.medworm.com/index.php?rid=3264415&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003749%2Fabstract%3Frss%3Dyes The mevalonate pathway plays an important role in myeloma cell survival. Conversion of HMG-CoA into mevalonate by HMG-CoA reductase is the rate-limiting step in producing cholesterol and is crucial for membrane and steroid synthesis. In addition, mevalonate is the precursor of other non-sterol products, including dolichol required for glycoprotein synthesis, ubiquinone involved in oxidative respiration, and the isoprenoids geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264415 Fri, 12 Feb 2010 14:22:41 +0100 3264415 http://www.medworm.com/index.php?rid=3264414&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212610000378%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3264414 Fri, 12 Feb 2010 14:22:41 +0100 3264414 http://www.medworm.com/index.php?rid=3221892&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003531%2Fabstract%3Frss%3Dyes Abstract: Background and objectives: The treatment of choice for the pregnant woman with CML has not been defined. Exposure to imatinib while pregnant may cause serious fetal malformations and interferon-α is sometimes associated with side effects. Furthermore, little is known of the possibility that BCR/ABL-positive cells might be passed to the fetus and the role of the treatment given to the pregnant mother.Design and methods: Detection of BCR-ABL transcripts in the peripheral blood of the mother, the newborn and the cord blood was performed by quantitative real time PCR and FISH.Results: A patient with CML diagnosed at the beginning of pregnancy was treated with leukapheresis at 31 weeks of gestation until delivery without any untoward effects. Since no tyrosine kinase inhibitor was ad... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221892 Sat, 30 Jan 2010 14:33:23 +0100 3221892 http://www.medworm.com/index.php?rid=3221891&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004457%2Fabstract%3Frss%3Dyes Chronic myeloid leukemia (CML) is a clonally hematologic malignant disease arising in the stem-cell compartment. Patients with CML show considerable heterogeneity both in their presenting clinical features and in the time taken for evolution to blast crisis . Herein we report the unusual case of a patient with Ph chromosome-positive CML who achieved complete hematological response and a long survival of 32 years with indirubin and its derivative, meisoindigo, treatment. During that long period the white blood cell count was stable and no progression of the disease was noted, whereas Philadelphia chromosome was detectable. Imatinib was given resulting in a complete cytogenetic response 3 months later. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221891 Sat, 30 Jan 2010 14:33:23 +0100 3221891 http://www.medworm.com/index.php?rid=3221890&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004421%2Fabstract%3Frss%3Dyes Comorbidities are coexisting diseases that are distinct from the primary illness for which a patient seeks health care services . Comorbidity may affect detection, prognosis, therapy, and outcome of the primary disease. We recently published a paper evaluating the role of comorbidities in the survival of patients with myelodysplastic syndromes, in which Charlson index was utilized as the measure of comorbidities . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221890 Sat, 30 Jan 2010 14:33:23 +0100 3221890 http://www.medworm.com/index.php?rid=3221889&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004317%2Fabstract%3Frss%3Dyes There have been several reports of patients with two hematopoietic neoplasms, one showing B-cell differentiation and the other being a histiocytic (H) or dendritic cell (DC) sarcoma (). It is intriguing that the two neoplasms have been found to be clonally related in all cases with clonality studies reported. We recently evaluated a patient who developed histiocytic sarcoma following treatment for precursor B-cell acute lymphoblastic leukemia (B-ALL) and demonstrated that the two neoplasms were clonally related. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221889 Sat, 30 Jan 2010 14:33:23 +0100 3221889 http://www.medworm.com/index.php?rid=3221888&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004263%2Fabstract%3Frss%3Dyes Refractory anaemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) is a provisional entity within the World Health Organization category myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN,U) . JAK2V617F mutation is found in virtually all patients with polycythemia vera (PV) and in approximately 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PM) . About 50% of patients with RARS-T also display JAK2V617F mutation : this suggests that RARS-T may constitute another JAK2 mutation-associated form of MPN . Interestingly, it was shown that patients with RARS-T and JAK2V617F mutation have a more favourable prognosis than those without the mutation . However, we have recently seen a patient with JAK2V617F positive RARS-T transfo... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221888 Sat, 30 Jan 2010 14:33:23 +0100 3221888 http://www.medworm.com/index.php?rid=3221887&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004159%2Fabstract%3Frss%3Dyes The few available studies on leukemia patients have so far addressed only the issue of physical pain and emotional distress in terminally ill patients The prevalence of pain during the last 3 months of life of Italian cancer patients was reported to be 83% in lymphoma and leukemia patients, according to what reported by their caregivers . This result is much higher compared with other studies reporting a prevalence of 5% in leukemia and 38% in lymphoma patients . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221887 Sat, 30 Jan 2010 14:33:23 +0100 3221887 http://www.medworm.com/index.php?rid=3221886&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003920%2Fabstract%3Frss%3Dyes Hematological malignancies (HM) may be progressively complicating by debilitating deteriorations of the personal status, physical deconditioning and several forms of motor disability (MD), often leading to severe limitations in performing activities of daily living (ADL) and in the loss of the individual independence. Although several forms of MD are frequent complaints of HM patients, yet information regarding its origins frequency and management is relatively scarce and most published data on this issue comes indirectly from studies focusing on solid tumours . A large variety of disabling conditions, which may be related to disease activity and/or to treatments, may be observed in this setting. In order to address this issue, we evaluated the incidence of MD in a group of consecutive and... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221886 Sat, 30 Jan 2010 14:33:22 +0100 3221886 http://www.medworm.com/index.php?rid=3221885&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003786%2Fabstract%3Frss%3Dyes Chronic lymphocytic leukemia (CLL) patients are prone to various complications, such as infections, autoimmune diseases (AID), second tumors or transformations. CLL is the most frequent type of leukemia in the western world, but it is rarely seen in Asian countries . Very limited data published in Chinese patients with respect to the incidence rate, category and prognosis of CLL complications. To explore the characteristics of complications in Chinese CLL patients, 203 cases of CLL patients from the Institute of Hematology and Blood Diseases Hospital, Tianjin, China, from the year 2000 to 2007 were reviewed and followed-up retrospectively. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221885 Sat, 30 Jan 2010 14:33:22 +0100 3221885 http://www.medworm.com/index.php?rid=3221884&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003750%2Fabstract%3Frss%3Dyes Chromosomal translocation involving the MLL gene, located at 11q23, is the most frequent abnormality in hematological malignancies and more than 50 genes have been identified as MLL fusion partners. However, unifying leukemogenic properties of partner genes remain unclear. Here, we describe a novel MLL-AF1p/Eps15 (epidermal growth factor receptor pathway substrate 15) fusion variant in previously reported therapy-related acute lymphoblastic leukemia (ALL) patient and argue for the function of AF1p as MLL fusion partner gene. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221884 Sat, 30 Jan 2010 14:33:21 +0100 3221884 http://www.medworm.com/index.php?rid=3221883&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003762%2Fabstract%3Frss%3Dyes Micafungin, which is the class of echinocandin antifungal drugs that inhibit β-(1,3)-d-glucan synthesis that is the main composition element of fungal cell walls in the peculiarity and has an excellent antimycotic activity, possesses high effectiveness against invasive aspergillosis and Candida spp., it excels also in safety, and it is used for the management of fungal infections to neutropenic patients after intensive chemotherapy or hematopoietic stem cell transplantation. Nanri et al. recently reported 2 patients developing acute hemolysis followed by acute renal failure due to micafungin administration . They revealed that red blood cells (RBCs) caused agglutination by the mixture of micafungin and the patient's plasma samples in the indirect antiglobulin test (AGT). Acute hemolysis d... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221883 Sat, 30 Jan 2010 14:33:21 +0100 3221883 http://www.medworm.com/index.php?rid=3221882&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003609%2Fabstract%3Frss%3Dyes Lymphoplasmacytic lymphoma (LPL) is a lymphoproliferative disorder which usually has an indolent course . We recently observed a leukemic form of LPL with a very aggressive clinical course and with massive skin infiltration. A 44-year-old woman was under observation because of malaise and fatigue as result of a moderate pancytopenia. She presented with pallor and poor clinical general condition. Her past history was not contributory. Physical exam revealed no remarkable findings; in particular, no superficial lymph nodes were palpable. A whole body computed tomography (CT) scan showed multiple enlarged adenopathies but no bulky localization. The laboratory evaluation showed moderate pancytopenia and a monoclonal paraprotein (2g/dL, IgG-k isotype); serum calcium and comprehensive metabolic ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221882 Sat, 30 Jan 2010 14:33:21 +0100 3221882 http://www.medworm.com/index.php?rid=3221881&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002264%2Fabstract%3Frss%3Dyes We describe here a unique chromosomal abnormality found in a patient with M3r subtype of APL. Neither t(15;17) nor rearrangement of RARα was detected by routine R-banded chromosome as well as fluorescence in situ hybridization (FISH) analysis using PML/RARα dual-color dual-fusion translocation probe and RARα dual-color break apart rearrangement probe. Instead of the typical rearrangement between chromosomes 15 and 17, all cells analyzed had a translocation between X and 17 as the sole karyotypic anomaly. The translocation was conformed by whole chromosome painting (WCP) with painting probes of chromosomes X and 17. To our knowledge, this is the first documented APL with a novel translocation involving chromosomes X and 17 without RARα gene rearrangement. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221881 Sat, 30 Jan 2010 14:33:20 +0100 3221881 http://www.medworm.com/index.php?rid=3221880&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003506%2Fabstract%3Frss%3Dyes We report a case of C-ALCL presenting with hemophagocytic syndrome and skin lesion with giant ulcer. Histopathological examination of the skin biopsy specimens showed non-epidermotropic infiltrates with cohesive sheets of large tumor cells. The tumor cells showed CD4−, CD8+, CD30+, CD56−, ALK−, TIA-1+, and granzyme B+. C-ALCL is generally a disorder that progresses slowly and has a good prognosis. Manifestation of a giant ulcer and hemophagocytic syndrome, such as in the present case, is rare. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221880 Sat, 30 Jan 2010 14:33:20 +0100 3221880 http://www.medworm.com/index.php?rid=3221879&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004792%2Fabstract%3Frss%3Dyes Abstract: Nucleophosmin 1 (NPM1), a protein that shuttles between the nucleus and cytoplasm, is mostly located in nucleoli. This is a multifunctional phosphoprotein to which both tumor-suppressor and oncogenic functions have been attributed. Here, we have found the cell line with the type A NPM1 mutation and with the other genetic alterations including ETV6-NTRC fusion. It will provide a good in vitro model for bio-molecular studies of interaction of mutated NPM1 gene and other genetic abnormalities as well as a useful tool for developing new molecularly targeted drugs. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221879 Sat, 30 Jan 2010 14:33:17 +0100 3221879 http://www.medworm.com/index.php?rid=3221878&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005232%2Fabstract%3Frss%3Dyes Abstract: To study the incidence of telomerase gene mutations in Chinese patients with acquired bone marrow failure (BMF) and explore its relationship with telomere shortening. Blood samples from 66 patients with aplastic anemia (AA) in northern China were collected and TERC mutation analysis was performed. Two TERC mutations were identified. The incidence of telomerase gene mutations in Chinese people with acquired AA is similar to that of the western people. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221878 Sat, 30 Jan 2010 14:33:16 +0100 3221878 http://www.medworm.com/index.php?rid=3221877&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900486X%2Fabstract%3Frss%3Dyes Abstract: Using gene expression profiling we show that the expression of 105-probe sets in mononuclear cells collected from chronic myeloid leukemia (CML) chronic phase (CP) patients with raised leukocyte counts who subsequently achieved complete cytogenetic response after 12 months on imatinib, differed substantially from that of patients who failed to achieve any degree of cytogenetic response. In the non-responder cohort, 9 of the 50 overexpressed genes were involved in DNA repair by homologous recombination, whereas 36 genes, including PTEN, were downregulated. This pattern of altered gene expression in responders and non-responders was validated in another independent dataset. These findings may prove useful for identifying at the time of diagnosis a subset of CP-CML patients who are ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221877 Sat, 30 Jan 2010 14:33:16 +0100 3221877 http://www.medworm.com/index.php?rid=3221876&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004883%2Fabstract%3Frss%3Dyes Abstract: Inhibition of cyclooxygenase 2 (COX-2) by the selective COX-2 inhibitor celecoxib has been suggested as potentially useful for B-cell lymphoma therapy. However, additional pharmacological activities of celecoxib have been discovered and have challenged the notion that its antitumor effects are mediated primarily via the inhibition of COX-2. To shed light on this issue, we have investigated the effects of different pharmacological agents with greatly varying COX-2 inhibitory potency in Raji lymphoma cells in vitro. We found that cytotoxic potency of these compounds did not at all correlate with their COX-2 inhibitory activity; in fact, the most potent COX-2 inhibitors lacked the ability to kill Raji cells. Instead, the cytotoxic outcome was closely aligned with these agents’ abi... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221876 Sat, 30 Jan 2010 14:33:16 +0100 3221876 http://www.medworm.com/index.php?rid=3221875&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003622%2Fabstract%3Frss%3Dyes Abstract: Bortezomib and Lenalidomide have been shown to be effective in the control of multiple myeloma (MM) progression. We have investigated their role in the in vitro expression of Osterix by primary osteoblast cultures from MM patients and found that Osterix RNA was constitutively down-regulated in these cells. Treatment of osteoblasts with Bortezomib resulted in an increase of Osterix RNA and in enhanced activity of both BMP-2 and Runx2. Instead, Lenalidomide was unable to modify Osterix transcription. These findings provide additional evidence suggesting that, at least in vitro, Bortezomib promotes the osteoblast maturation whereas Lenalidomide is ineffective. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221875 Sat, 30 Jan 2010 14:33:16 +0100 3221875 http://www.medworm.com/index.php?rid=3221874&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002653%2Fabstract%3Frss%3Dyes In this study, we investigated whether VPA influences CXCR4 in CD34-negative AML cell lines (promyelocytic HL-60 and monocytic THP-1), as well as both CD34-positive and CD34-negative primary AML cells. We found that VPA (i) diminishes CXCR4 expression and chemotaxis in HL-60 cells and in the CD34-negative subtypes of primary AML cells and (ii) increases CXCR4 expression and function in the highly CD34-positive subtypes of primary AML cells. Hence, we suggest that VPA exerts different effects on CXCR4 depending on cell maturation status, and this novel finding may have important implications for AML therapy. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221874 Sat, 30 Jan 2010 14:33:16 +0100 3221874 http://www.medworm.com/index.php?rid=3221873&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002665%2Fabstract%3Frss%3Dyes Abstract: Although clearly effective in acute promyelocytic leukemia (APL), arsenic trioxide (ATO) demonstrates little clinical benefit as a single agent in the treatment of non-APL hematological malignancies. We screened a library of 2000 marketed drugs and naturally occurring compounds to identify agents that potentiate the cytotoxic effects of ATO in leukemic cells. Here, we report the identification of three isothiocyanates (sulforaphane, erysolin and erucin) found in cruciferous vegetables as enhancers of ATO cytotoxicity. Both erysolin and sulforaphane significantly enhanced ATO-mediated cytotoxicity and apoptosis in a panel of leukemic cell lines; erucin activity was variable among cell types. Cellular exposure to sulforaphane in combination with ATO resulted in a dramatic increase ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221873 Sat, 30 Jan 2010 14:33:16 +0100 3221873 http://www.medworm.com/index.php?rid=3221872&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003713%2Fabstract%3Frss%3Dyes In conclusion, JNJ-26481585 is a potent second-generation pan-HDAC inhibitor with activity in human leukemia, and it is currently in clinical development. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221872 Sat, 30 Jan 2010 14:33:16 +0100 3221872 http://www.medworm.com/index.php?rid=3221871&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002847%2Fabstract%3Frss%3Dyes Abstract: Mutations in the BLM gene cause human Bloom syndrome (BS), an autosomal recessive disorder of growth retardation, immunodeficiency and cancer predisposition. Homozygous null Blmm3/m3 mice are cancer prone with a 5-fold increased risk of cancer compared with Blmm3/+ and Blm+/+ mice. Irradiation of Blmm3/m3 mice increased the risk to 28-fold. Tumors occurred mainly in the hematopoietic system and were similar to those in BS based on detailed histologic and immunohistochemical analyses. Irradiated Blm-deficient mice thus provide a novel model for understanding accelerated malignancies in BS and a new platform for investigating the molecular basis for a wide range of hematopoietic neoplasms. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221871 Sat, 30 Jan 2010 14:33:15 +0100 3221871 http://www.medworm.com/index.php?rid=3221870&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003439%2Fabstract%3Frss%3Dyes Abstract: Murine models of disease are vital to the understanding of pathogenesis and the development of novel therapeutics. We have previously established interleukin (IL)-15 transgenic (tg) mice that demonstrate rapid proliferation of natural killer (NK) and T cells, followed by spontaneous transformation to lethal leukemia. Herein, we have characterized this model, which has many features in common with the aggressive variants of NK and T large granular lymphocyte leukemia (LGLL) in humans. The LGLL blasts are cytolytic and produce IFN-γ ex vivo. Cytogenetic analysis revealed trisomy of chromosome 17 and/or 15. This model should provide opportunities to develop effective standard therapies for this fatal disease. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221870 Sat, 30 Jan 2010 14:33:15 +0100 3221870 http://www.medworm.com/index.php?rid=3221869&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003671%2Fabstract%3Frss%3Dyes Abstract: VEGFR and c-Kit signaling pathways may contribute to the pathophysiology of acute myeloid leukemia (AML). Thirty-five patients with AML received cediranib (RECENTIN™), an oral, highly potent VEGF signaling inhibitor with c-Kit activity, at doses of ≤30mg/day. The most common adverse events were diarrhea, hypertension and fatigue. Six patients experienced an objective response (3 each at 20 and 30mg). Dose- and time-dependent reductions in sVEGFR-2 were observed, and there was a positive correlation between cediranib exposure and the change in plasma VEGF levels from baseline. Cediranib was generally well tolerated and showed preliminary evidence of activity as a monotherapy. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221869 Sat, 30 Jan 2010 14:33:15 +0100 3221869 http://www.medworm.com/index.php?rid=3221868&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002604%2Fabstract%3Frss%3Dyes Abstract: We used fluorescence in situ hybridization (FISH) assays to identify t(14;18) translocations in archival paraffin-embedded tumor sections from non-Hodgkin lymphoma (NHL) cases enrolled in a population-based study. t(14;18) was identified in 54% of 152 cases, including 39% of diffuse large cell lymphomas (26 of 66 cases) and 84% of follicular lymphomas (36 of 43 cases). Eighty-seven percent of t(14;18)-positive cases and 57% of t(14;18)-negative cases expressed bcl-2. FISH assays detected twice as many t(14;18)-positive follicular lymphomas as PCR assays. Overall, study findings support the use of FISH assays to detect t(14;18) in archival tumor samples for epidemiologic studies of NHL subtypes. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221868 Sat, 30 Jan 2010 14:33:15 +0100 3221868 http://www.medworm.com/index.php?rid=3221867&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609001830%2Fabstract%3Frss%3Dyes Abstract: Standard chemotherapic approach for MZL is missing. We are presenting our monocenter experience with 2CdA±rituximab.Patients received 2CdA, 5mg/m2, weekly, for 6 weeks. Patients receiving rituximab underwent to antibody administration in association with 2CdA, or after the end of chemotherapy.Global ORR was 89.3%, with 53.6% CR, with 60 months of median of TTF.2CdA and rituximab led to 96.5% ORR, with 60.3% CR, while 2CdA alone to 73.1% ORR, with 38.5% CR. TTF median was reached at 35 months with 2CdA alone; not reached yet in the combination arm.Considering subgroups of MZL, combination therapy has a more favorable outcome in SMZL and NMZL, while MALT does not differ. However, all subgroups present a delayed relapse.Considering minimal residual disease (MRD), adding of rituxima... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221867 Sat, 30 Jan 2010 14:33:15 +0100 3221867 http://www.medworm.com/index.php?rid=3221866&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002859%2Fabstract%3Frss%3Dyes Abstract: Telomerase activity has been found in most common cancers, thus indicating that telomerase detection may be a useful marker in cancer diagnosis. The telomeric amplification protocol (TRAP) assay and RT-PCR are customarily used to detect telomerase activity and the expression of the associated genes in cells. However, these methods do not provide any information about telomerase activation at an individual cell level. To analyze cells separately, those cells have to be isolated by sometimes complicated method. The immunohistochemical detection of human telomerase reverse transcriptase (hTERT) is useful to detect telomerase positive cells in a background of non-cancerous cells.A method has been developed for the detection of intranuclear hTERT protein, in a subpopulation of hematop... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221866 Sat, 30 Jan 2010 14:33:14 +0100 3221866 http://www.medworm.com/index.php?rid=3221865&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003774%2Fabstract%3Frss%3Dyes Abstract: Tissue-based determination of Ki-67, a marker of cellular proliferation, has shown prognostic value in solid tumors and hematological malignancies. We developed and validated an electrochemiluminescence-based method for sensitive measurement of circulating Ki-67 in plasma (cKi-67). This assay demonstrated significantly higher levels of cKi-67 in patients with newly diagnosed acute lymphoblastic leukemia (ALL) (n=27; median, 762; range, 0–4574U/100μL) than in healthy control subjects (n=114; median, 399; range, 36–2830U/100μL). Moreover, elevated plasma cKi-67 was associated with significantly shorter survival in ALL patients (P=0.05). These findings suggest that Ki-67 can be detected in circulation and has potential for use as a biomarker for predicting clinical behavior in... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221865 Sat, 30 Jan 2010 14:33:14 +0100 3221865 http://www.medworm.com/index.php?rid=3221864&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002586%2Fabstract%3Frss%3Dyes Abstract: The Bcl-2 protein inhibits apoptosis (programmed cell death) of hematopoietic stem cells induced by a variety of noxious stimuli, thus mediating chemoresistance and decreasing chemosensitivity. Higher Bcl-2 expression correlates to an adverse outcome following therapy for acute myeloid leukemia (AML). The current study determined whether a BCL2 gene single nucleotide polymorphism (SNP) could affect treatment outcomes in 99 AML patients excluding acute promyelocytic leukemia. Two genotypes were tested, including BCL2 −938 C>A (rs2279115) and +21 A>G (rs1801018). Neither the −938 C>A nor the +21 A>G BLC2 genotype was associated with complete remission (CR) rates following chemotherapy. The −938 A>C BCL2 genotype did not affect leukemia-free survival (LFS), event-free survival... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221864 Sat, 30 Jan 2010 14:33:14 +0100 3221864 http://www.medworm.com/index.php?rid=3221863&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003579%2Fabstract%3Frss%3Dyes Abstract: Karyotype status and complexity are key components of the IPSS; however, emerging data suggest the use of cytogenetics at disease presentation is not applied uniformly among MDS patients. To investigate the degree of consistency of scoring karyotypes, the International Working Group on MDS Cytogenetics (IWGMC) conducted a survey of 32 abnormal karyotype challenges carried out in two phases: (a) an initial survey without any specified karyotype counting guidelines and (b) a second survey conducted after the development of IWGMC consensus guidelines for scoring karyotype complexity. Results indicate that IWGMC guidelines were simple and clear for the cytogeneticists in scoring karyotype complexity, but not as clear for the hematologists. We propose an immediate need for standardize... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221863 Sat, 30 Jan 2010 14:33:14 +0100 3221863 http://www.medworm.com/index.php?rid=3221862&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002203%2Fabstract%3Frss%3Dyes Conclusion: Our data did not show that CYP3A5, MDR-1 or MAPT polymorphisms are linked to impaired motor performance in children after treatment for ALL. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221862 Sat, 30 Jan 2010 14:33:14 +0100 3221862 http://www.medworm.com/index.php?rid=3221861&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002963%2Fabstract%3Frss%3Dyes Abstract: Methylation is now established as a fundamental regulator of gene transcription. To investigate this in haematologic malignancies, we evaluated the aberrant promoter methylation of two imprinted genes (MEG3 and SNRPN) in 43 MDS and 42 AML patients. MEG3 hypermethylation occurred in 15 MDS patients (34.9%), and in 20 AML patients (47.6%). SNRPN hypermethylation was observed in 15 MDS patients (34.9%), and in 21 AML patients (50%). There were no significant correlations between WHO subtype, WPSS score, karyotype, haemoglobin levels, white blood cell count, platelet count and CpG methylation of any gene. MEG3 hypermethylation was associated with significantly reduced overall survival in individuals with AML (HR=1.98, p=0.04), while SNRPN CpG methylation was not associated with survi... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221861 Sat, 30 Jan 2010 14:33:14 +0100 3221861 http://www.medworm.com/index.php?rid=3221860&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002446%2Fabstract%3Frss%3Dyes Abstract: Philadelphia-positive chronic myeloid leukemia (Ph+ CML) patients who are resistant to imatinib are commonly treated with second-generation tyrosine kinase inhibitors (TKIs). Limited data exist on the possible effects of these drugs on subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT).The outcome of 12 imatinib-resistant CML patients treated with dasatinib or nilotinib or both before allo-HSCT, was retrospectively analyzed.Patients were treated with second-generation TKIs for 1–17 months (median, 8). At the time of transplant, 3 patients were in complete cytogenetic response (CCgR), 3 patients in partial cytogenetic response (PCgR) and 6 patients were in less than PCgR. Donors were HLA-matched related in 4 cases and unrelated in 8 cases. Stem cell source... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221860 Sat, 30 Jan 2010 14:33:13 +0100 3221860 http://www.medworm.com/index.php?rid=3221859&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003889%2Fabstract%3Frss%3Dyes Inherited predisposition to MDS and/or AML is rare but investigation of families with these conditions has provided valuable insight into the pathogenesis of leukemia. To date, only 2 gene mutations, CEBPA and RUNX1, have been causally linked to predisposition for MDS/AML . While families with germline CEBPA mutations display no warning features prior to the development of AML, individuals with germline RUNX1 mutations usually present with thrombocytopenia and/or platelet function abnormalities, leading to a clinical diagnosis of Familial Platelet Disorder with Propensity to Myeloid Malignancy (FPD/AML) that can be evident before the onset of overt malignancy. However, the clinical history is incredibly variable with many individuals displaying no platelet abnormalities prior to the onset ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221859 Sat, 30 Jan 2010 14:33:13 +0100 3221859 http://www.medworm.com/index.php?rid=3221858&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003683%2Fabstract%3Frss%3Dyes DNA methylation, amongst the known epigenetic modifications, appears to play a crucial role in leukaemogenesis. Both acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) have a high prevalence of methylation in various genes including those encoding for p15INK4B, p21CIP1/WAF1, the oestrogen receptor, CALC1, HIC-1, E-Cadherin and others. Furthermore, progression of MDS and AML is associated with an increased rate of methylation at key promoter regions, and survival in patients with AML and MDS with genomic DNA hypermethylation is significantly reduced compared to those with no abnormal DNA methylation. Since the importance of DNA methylation in disease pathogenesis of AML and MDS is becoming more accepted, promising new approaches to target and reverse DNA methylation have been... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221858 Sat, 30 Jan 2010 14:33:13 +0100 3221858 http://www.medworm.com/index.php?rid=3221857&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003695%2Fabstract%3Frss%3Dyes The introduction of the tyrosine kinase inhibitor (TKI), imatinib mesylate, has revolutionized the treatment of chronic myeloid leukemia (CML) . Its remarkable efficacy and relative lack of toxicity have established it as the initial therapy for all patients with CML. The remarkable saga of its development from the discovery of the Philadelphia chromosome in 1961 with the subsequent identification of the BCR-ABL tyrosine kinase as the molecular event that is causative of CML has been recently chronicled . Before the imatinib era, a small minority of patients were also able to achieve major cytogenetic responses with interferon alpha. Patients who were transplant eligible and had a suitable donor were considered for allogenic blood or marrow transplant (BMT). Even after the introduction of ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221857 Sat, 30 Jan 2010 14:33:13 +0100 3221857 http://www.medworm.com/index.php?rid=3221856&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004135%2Fabstract%3Frss%3Dyes Abstract: The TCL1 mouse has been proposed as a mouse model for chronic lymphocytic leukemia. This review details how it resembles the aggressive form of the disease rather than the more common indolent form. Although fulfilled predictions in the human disease based on investigations in the mouse model are at present lacking, there are remarkable similarities between human and mouse leukemias that have led to interesting observations on the pathophysiology of chronic lymphocytic leukemia and have identified putative therapeutic targets. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221856 Sat, 30 Jan 2010 14:33:13 +0100 3221856 http://www.medworm.com/index.php?rid=3221855&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004408%2Fabstract%3Frss%3Dyes Abstract: Imatinib mesylate is currently the standard of care for chronic myeloid leukemia (CML) patients in early chronic phase. However, the emergence of resistance and intolerance has dampened the enthusiasm for this drug. To overcome this phenomenon, different strategies have been developed, including novel targeted agents. Nilotinib, formerly known as AMN107, is a second-generation tyrosine kinase inhibitor 30-fold more potent than imatinib, with high affinity and selectivity on BCR/ABL, and also active against a wide range of mutant clones, except T315I mutation. Phase II trials of nilotinib showed high activity in imatinib-resistant or intolerant CML patients, whereas front-line treatment of the disease in chronic phase demonstrated rapid and stable cytogenetic responses and increas... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221855 Sat, 30 Jan 2010 14:33:13 +0100 3221855 http://www.medworm.com/index.php?rid=3221854&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212610000160%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3221854 Sat, 30 Jan 2010 14:33:13 +0100 3221854 http://www.medworm.com/index.php?rid=3134589&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004469%2Fabstract%3Frss%3Dyes Extranodal natural killer/T-cell lymphoma, nasal type, or nasal NK/T-cell lymphoma is an extranodal lymphoma usually with an immature natural killer (NK)-cell phenotype and Epstein-Barr virus positivity. It is commonly present in the midfacial region, but can occur in other extranodal sites . There is a broad morphologic spectrum, frequently characterized by necrosis and angioinvasion. The immunophenotype of this lymphoma is either NK or NK/T-cell type. Most cases, especially in Asia, are EBV positive. Extranodal NK/T-cell lymphoma is a rare disorder in the United States and Europe, comprising (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134589 Fri, 01 Jan 2010 00:00:00 +0100 3134589 http://www.medworm.com/index.php?rid=3134588&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004378%2Fabstract%3Frss%3Dyes Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening condition characterized by uncontrolled hyperinflammation on the basis of various inherited or acquired immune deficiencies . It is a histiocytic reactive process frequently associated with infections and malignancies in the patients with non-inherited genetical abnormalities. The malignancy-associated hemophagocytic lymphohistiocytosis is usually associated with T-cell lymphoma . An association with acute myeloid leukemia (AML) is a rare event, only two cases have been reported who presented with HLH and then developed AML . Here, we describe a case of HLH who first presented with normal karyotype and partially remitted since the initiation of immunosuppressive therapy for more than 3 months, however, HLH eventually relapsed an... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134588 Fri, 01 Jan 2010 00:00:00 +0100 3134588 http://www.medworm.com/index.php?rid=3134587&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004329%2Fabstract%3Frss%3Dyes Castleman disease (CD), also known as angiofollicular lymph node hyperplasia, was first described in 1954 by Dr. Benjamin Castleman . Although the etiology and pathogenesis is not fully understood, it has been associated with human immunodeficiency virus (HIV) and human herpes virus-8; in addition, interleukin-6 has been found to play a role in many cases of CD . CD is classified by histological type and location of the disease . Multicentric CD (MCD) is a plasma cell variant predominantly, with some cases with plasmablastic characteristics . MCD has a variable clinical course and may be progressive over months or episodic with recurrent exacerbations over years. The plasma cell type of CD has a poorer prognosis and more systemic manifestations. Clinical findings such as fever, night sweat... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134587 Fri, 01 Jan 2010 00:00:00 +0100 3134587 http://www.medworm.com/index.php?rid=3134586&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900438X%2Fabstract%3Frss%3Dyes In the recent issue, we have reported two cases of myelodysplastic syndrome (MDS) with a novel unbalanced whole-arm translocation der(5;19)(p10;q10) . This translocation was accompanied by an additional normal chromosome 19 and described as der(5;19)(p10;q10),+19, which resulted in monosomy 5q and trisomy 19q. Furthermore, both patients presented several common clinical and hematological findings. That is, MDS subtypes were advanced stage, refractory anemia with excess blasts (RAEB)-1 and RAEB-2. Peripheral blood showed leukoerythroblastosis, and marked anemia and thrombocytopenia without neutropenia. Bone marrow demonstrated trilineage dysplasia with prominent dyserythropoiesis. Myeloblasts expressed CD7 as well as myeloid markers. Besides der(5;19),+19, additional cytogenetic aberrations... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134586 Fri, 01 Jan 2010 00:00:00 +0100 3134586 http://www.medworm.com/index.php?rid=3134585&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004330%2Fabstract%3Frss%3Dyes Fibrosis of the bone marrow is a pathological condition associated with a variety of bone marrow neoplasms, including, for example, myeloproliferative neoplasms (MPN), acute megakaryoblastic leukemia, and hairy cell leukemia. Bone marrow fibrosis can also be seen with infections of the bone marrow, such as tuberculosis, or associated with metastatic disease in the bone marrow from solid tumors . In cases where a cause for bone marrow fibrosis cannot be readily identified, primary myelofibrosis (PMF) is frequently diagnosed. Histological features of bone marrow in PMF include significant deposits of extracellular matrix proteins, increased angiogenesis, osteosclerosis and increased hematopoiesis . Patients with PMF usually present with anemia, peripheral blood smear showing teardrop red cel... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134585 Fri, 01 Jan 2010 00:00:00 +0100 3134585 http://www.medworm.com/index.php?rid=3134584&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004202%2Fabstract%3Frss%3Dyes Non-Hodgkin's lymphoma (NHL) presenting with diabetes insipidus (DI) in consequence of hypophyseal lesion is relatively rare. The condition may occur as either primary central nervous system (CNS) lymphoma or systemic lymphoma with meningeal or parenchymal involvement . As the latter, it is more often in intermediate and high grade malignant NHL . Although a few unusual localizations in CNS have been reported, the data about pituitary involvement with DI as first complaint of NHL is very limited. Here, we report on two cases who complained of DI before NHL was diagnosed. Brain MRI showed absence of the normal hyperintense signal at the posterior lobe of the pituitary in both cases, slight enlargement of the pituitary stalk in one patient with Burkitt lymphoma, and an empty sella with defor... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134584 Fri, 01 Jan 2010 00:00:00 +0100 3134584 http://www.medworm.com/index.php?rid=3134583&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004184%2Fabstract%3Frss%3Dyes Secondary hematological malignancies have been increasingly reported as an important late complication in patients with various malignant diseases, and their direct relationship with radiotherapy and chemotherapy treatment . On rare occasions, some patients only received surgical management or without prior therapy for their primary malignancies. To our knowledge, only 12 cases of non-therapy-related acute lymphoblastic leukemia (nTr-ALL), defined as ALL following another malignancy only received surgical management or without prior therapy, are reported in the literature . Here, we report a novel case of nTr-ALL with t(9;22)(q34;q11) in a patient with primary uterine leiomyosarcoma, and discuss the biologic and clinical characteristics of this phenomenon. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134583 Fri, 01 Jan 2010 00:00:00 +0100 3134583 http://www.medworm.com/index.php?rid=3134582&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004147%2Fabstract%3Frss%3Dyes It has now become clear that most Chronic Myeloid Disorders (CMD) are hematological malignancies originating from a primary oncogenic event. Chronic myeloid leukemia (CML) is characterized by the Philadelphia (Ph) chromosome resulting from the reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11). The classic BCR–ABL gene of CML results from the fusion of parts of the ABL gene on chromosome 9 and the BCR gene on chromosome 22. The breakpoints usually occur simultaneously in exon a2 of the ABL gene and exons e12–e16 (b1–b5) of the BCR gene, resulting in a hybrid BCR–ABL fusion gene with either b2a2 or b3a2 junctions which are subsequently translated into the oncoprotein p210BCR–ABL. In rare cases of CML, there are variant breakpoints on the BCR gene, resulting i... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134582 Fri, 01 Jan 2010 00:00:00 +0100 3134582 http://www.medworm.com/index.php?rid=3134581&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004238%2Fabstract%3Frss%3Dyes Arsenic trioxide (ATO) is an effective drug for patients with acute promyelocytic leukemia (APL) that is resistant to all trans-retinoic acid and anthracycline chemotherapy . Pleural and/or pericardial effusion in patients undergoing ATO treatment has been reported, and APL differentiation syndrome or generalized fluid retention has been considered to be the pathophysiology in most cases. Here, we report a case of APL who developed pleural and pericardial effusion during ATO treatment through a different pathological mechanism. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134581 Fri, 01 Jan 2010 00:00:00 +0100 3134581 http://www.medworm.com/index.php?rid=3134580&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003737%2Fabstract%3Frss%3Dyes We report another case of ECD treated with IFN-α and discuss the therapeutic efficacy. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134580 Fri, 01 Jan 2010 00:00:00 +0100 3134580 http://www.medworm.com/index.php?rid=3134579&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003804%2Fabstract%3Frss%3Dyes Primary hepatic lymphoma is a rare disease. Primary low-grade lymphoma of the liver is uncommon and accounts for less than 1% of all cases of extranodal lymphoma . Most cases of hepatic lymphoma represent the secondary involvement of intermediate or high-grade non-Hodgkin's lymphoma . Similar to extranodal lymphomas from other anatomic regions, most primary hepatic lymphomas are diffuse large B cell lymphomas . Primary hepatic marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was first introduced in 1995. These lymphomas are often associated with a history of chronic inflammation or autoimmune disease . In this case report, we describe a woman with primary hepatic MALT lymphoma associated with primary biliary cirrhosis (PBC). (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134579 Fri, 01 Jan 2010 00:00:00 +0100 3134579 http://www.medworm.com/index.php?rid=3134578&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003798%2Fabstract%3Frss%3Dyes The recurring chromosome abnormalities involving special genes are closely associated with the distinct subsets of leukemia with morphological, immunophenotypic and clinical features. The t(l;19)(q23;pl3) structurally interrupts the E2A gene located at 19p13, which codes for the helix-loop-helix transcription factors E12 and E47, and fuses it to the chromosome 1 gene PBX1 for a homeobox gene . The translocation leads to product a novel E2A/PBX1 chimeric transcription factors . It was demonstrated that E2A–PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family . The t(l;19)(q23;pl3), the one of the frequent recurring translocation in childhood ALL, is present in about 5% of ALL cases, including 20–25% of ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134578 Fri, 01 Jan 2010 00:00:00 +0100 3134578 http://www.medworm.com/index.php?rid=3134577&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003634%2Fabstract%3Frss%3Dyes T-cell acute lymphoblastic leukemia (T-ALL) is genetically highly heterogeneous. Oncogenes transcriptionally activated in T-ALL, include TAL1, TLX1, TLX3, HOXAs, and fusion genes, such as MLL fusions are also observed. In addition, the tumor suppressor locus CDKN2A/P16/ARF is targeted in most T-ALL cases, and the NOTCH1 gene is activated by point mutations in more than 50% of T-ALL . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134577 Fri, 01 Jan 2010 00:00:00 +0100 3134577 http://www.medworm.com/index.php?rid=3134576&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003440%2Fabstract%3Frss%3Dyes In contrast to four recently published cases of syndromic thrombocytopenia with constitutional 21q22 RUNX1 deletions by Shinawi et al. and Beri-Dexheimer et al. , we describe a constitutional 21q22 microdeletion (including RUNX1) presenting as non-syndromic congenital thrombocytopenia with myelodysplasia. The former cases showed variable degrees of dysmorphic features, short stature and mental retardation (MR), suggesting a dosage-sensitive causative role of gene(s) on 21q22 in MR. One patient had developed myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) at the age of 6 years. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134576 Fri, 01 Jan 2010 00:00:00 +0100 3134576 http://www.medworm.com/index.php?rid=3134575&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003919%2Fabstract%3Frss%3Dyes Imatinib inhibits the tyrosine kinase functions of BCR-ABL, platelet-derived growth factor receptor, and c-kit receptor associated with specific diseases, and is a first-line treatment in patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour . Recent studies demonstrated a protective effect of imatinib on type 2 and type 1 diabetes in rodents. Clinical findings, showing that CML patients on imatinib therapy improved their type 2 diabetes , and hypoglycemic episodes with increased insulin response after an oral glucose tolerance test (OGTT) in a non-diabetic patient during imatinib treatment , suggested that imatinib might act peripherally to enhance insulin sensitivity. These evidences led to the hypothesis that imatinib-like drugs could be generated to develop ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134575 Fri, 01 Jan 2010 00:00:00 +0100 3134575 http://www.medworm.com/index.php?rid=3134574&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002148%2Fabstract%3Frss%3Dyes This study describes a patient with a relapsed, diffuse, large B cell lymphoma (DLBCL) treated with radioimmunotherapy (RIT) with yttrium-90 (90Y)-ibritumomab tiuxetan (Zevalin®) who 5 months later developed acute myeloid leukemia (AML) with inversion of chromosome 16. Our data indicate that molecular biological techniques should be used in selected cases to integrate data obtained with standard cytogenetics: using RT-PCR we showed that inversion of chromosome 16 was already present before RIT, in striking contrast to the normal karyotype found with conventional cytogenetics. This approach will allow investigators to avoid misleading data and provide support for conclusions regarding the side effects of treatment. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134574 Fri, 01 Jan 2010 00:00:00 +0100 3134574 http://www.medworm.com/index.php?rid=3134573&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003543%2Fabstract%3Frss%3Dyes We describe a patient with CML who developed renal failure during IM treatment which resolved upon discontinuation of the drug and was not exacerbated by the administration of nilotinib.The literature reporting on the association between TKIs and renal failure is reviewed and the postulated mechanisms including tubular dysfunction caused by the drug or tumor lysis syndrome are discussed. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134573 Fri, 01 Jan 2010 00:00:00 +0100 3134573 http://www.medworm.com/index.php?rid=3134572&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003816%2Fabstract%3Frss%3Dyes In this study, we tested if FLT3/internal tandem duplication (ITD) in acute myeloid leukemia (AML) might occur at different hierarchical stages during leukemogenesis. In 56 AML cases, 10 showed FLT3/ITD (single ITD=5; multiple ITD=5). Myeloblasts from seven cases (CD34-selected=4; unselected=3) were transplanted into NOD/SCID mice. Five cases engrafted successfully into 14 mice. Two patients carried single FLT3/ITD subclones, which were maintained during primary and secondary transplantations. In three patients with multiple FLT3/ITD subclones, some subclones persisted or expanded while others diminished upon transplantation. Their different engraftment capabilities in NOD/SCID mice supported the proposition that FLT3/ITD might occur at different stages during leukemogenesis. (Source: Leuk... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134572 Fri, 01 Jan 2010 00:00:00 +0100 3134572 http://www.medworm.com/index.php?rid=3134571&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002732%2Fabstract%3Frss%3Dyes Bone marrow necrosis (BMN) is defined as necrosis of the medullary stroma and myeloid tissues in large areas of the hematopoietic bone marrow (BM) leaving an amorphous eosinophilic background, poorly defined necrotic cells and preserved cortical bone . It is associated with a poor prognosis . Hematologic malignancies, such as acute and chronic leukemia, Hodgkin's and non-Hodgkin's lymphoma, chronic myeloproliferative disorders, and some solid tumors are most commonly associated with BMN . A rare but life-threatening complication of BMN is the fat embolism syndrome (FES) . Fat globules or necrotic BM, after being embolized to the pulmonary arteries, can pass pulmonary capillaries, patent foramen ovale or arteriovenous shunts and enter the left circulation damaging organs. Fat embolism (FE) ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134571 Fri, 01 Jan 2010 00:00:00 +0100 3134571 http://www.medworm.com/index.php?rid=3134570&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003427%2Fabstract%3Frss%3Dyes Abstract: TEL-AML1 is an oncogenic fusion protein associated with childhood pre-B acute lymphoblastic leukaemia. From published microarray datasets we identified the Rho Guanine Nucleotide Exchange Factor (RhoGEF) Asef to be associated with TEL-AML1 leukaemia. However, the Asef gene is not a direct target of TEL-AML1 transcriptional control. Forced expression of Asef in vitro induced and maintained proliferation of haemaopoietic progenitor cells and co-operated with TEL-AML1 greatly to enhance proliferation and haemopoietic colony size. In haemopoietic transplantation reconstitution assays Asef and TEL-AML1 together failed to induce a leukaemic phenotype. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134570 Fri, 01 Jan 2010 00:00:00 +0100 3134570 http://www.medworm.com/index.php?rid=3134569&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002690%2Fabstract%3Frss%3Dyes Abstract: Mantle cell lymphoma (MCL) an incurable B-cell, non-Hodgkin lymphoma (NHL) urgently requires new treatments. We assessed reovirus mediated oncolysis in a panel of human MCL cell lines. In vitro, we found the cytopathic effect of reovirus infection ranged from high to very limited and correlated with levels of Ras activation. In vivo, a single reovirus injection intra-tumorally resulted in complete regression of both the injected and the contra-lateral tumor in a subcutaneous bi-tumor model, in one out of three cell lines tested. Reovirus treatment of MCL seems feasible but will need to be guided by the presence of molecular determinants of reovirus susceptibility. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134569 Fri, 01 Jan 2010 00:00:00 +0100 3134569 http://www.medworm.com/index.php?rid=3134568&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609001623%2Fabstract%3Frss%3Dyes Abstract: We demonstrate here that TPA activates HTLV-1 LTR expression in Jurkat and H9 T-cell lines, by strictly different mechanisms. In Jurkat cells this activation is exerted by a PKCα- and PKCɛ-antagonized mechanism which operates through an Sp1 binding site residing within the Est responsive region 1 of the LTR. On the other hand, in H9 cells TPA activates the LTR by two consecutive mechanisms; the first depends on PKCη activity and is exerted through the 21bp repeats of the LTR, whereas the second is analogous to that observed in Jurkat cells, except that it is antagonized by PKCδ. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134568 Fri, 01 Jan 2010 00:00:00 +0100 3134568 http://www.medworm.com/index.php?rid=3134567&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002756%2Fabstract%3Frss%3Dyes Abstract: The combination of ATO and bortezomib (ATO+bortezomib) has been recently shown to enhance antimyeloma activity; nevertheless, the mechanisms remained unclear in these studies. However, both bortezomib and ATO have been shown to activate the p38 MAPK pathway, which may counteract the enhancement induced by this combination. We studied the cytotoxicity of bortezomib, ATO, and ATO+bortezomib with or without inhibiting p38 MAPK, along with associated molecular changes in myeloma cells. The treatment of myeloma cells with ATO+bortezomib induced higher cytotoxicity than either agent alone. This increased cytotoxicity was further synergistically enhanced by inhibiting p38 MAPK. This effect was preserved in the presence of marrow stromal cells designed to simulate the tumor micro-environ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134567 Fri, 01 Jan 2010 00:00:00 +0100 3134567 http://www.medworm.com/index.php?rid=3134566&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004652%2Fabstract%3Frss%3Dyes In conclusion, combined PKA and pan-PPAR activation should be explored further to determine its therapeutic potential. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134566 Fri, 01 Jan 2010 00:00:00 +0100 3134566 http://www.medworm.com/index.php?rid=3134565&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609001490%2Fabstract%3Frss%3Dyes Abstract: Genistein combined polysaccharide (GCP), derived from soy bean extract, is comprised of deglycosylated isoflavones, such as genistein and daidzein. The goal of this work was to determine if GCP is effective in lymphoid cancers.In three human and four canine lymphoid cell lines, GCP inhibited proliferation and induced G2/M arrest. Additionally, increased apoptosis was observed in Ramos and Jurkat lines. These results demonstrate that GCP is effective in lymphoid cell lines of both human and canine origin. Due to its minimal toxicities, increased bioavailability, and in vitro efficacy, GCP may have clinical utility in the treatment of patients with lymphoma. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134565 Fri, 01 Jan 2010 00:00:00 +0100 3134565 http://www.medworm.com/index.php?rid=3134564&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609001660%2Fabstract%3Frss%3Dyes Abstract: Using array-based CGH, we identified 2p gain in 22/78 (28%) untreated Binet stages B/C CLL, which was the second most frequent copy number change after 13q deletion. It never occurred as a sole abnormality and was associated with other changes (6q deletion; 1p gain). The region of 2p gain frequently included two oncogenes, REL and MYCN. All patients with gain of REL were unmutated for IGHV (p=0.03). Gain of MYCN was associated with increased mRNA expression (p=0.005), suggesting a pathogenic role for MYCN. Gain of 2p appears to be a marker of progression and may contribute to the poor prognosis. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134564 Fri, 01 Jan 2010 00:00:00 +0100 3134564 http://www.medworm.com/index.php?rid=3134563&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609001453%2Fabstract%3Frss%3Dyes Conclusion: Outcome of MDS in the VA was similar to what is described in literature and reported by the SEER Program. Appropriate coding for WHO subtypes, IPSS and treatment details are needed in all MDS registries to facilitate comparisons across populations. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134563 Fri, 01 Jan 2010 00:00:00 +0100 3134563 http://www.medworm.com/index.php?rid=3134562&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900215X%2Fabstract%3Frss%3Dyes Abstract: Accumulating evidences suggest that killer cell immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of diverse kinds of diseases. However, the functions and effects of KIR gene polymorphisms in the development of diseases remain largely unknown, especially about the activating KIR genes. To investigate the association of KIR gene polymorphisms with subtypes of leukemia, we carried out the present study on 263 patients with leukemia and 239 healthy controls by means of polymerase chain reaction-sequence-specific primer and analysis, and then all data were analyzed by Logistic regression method. Our results showed that the frame genotypes of KIR2DL4, 3DL2, 3DL3 and 3DP1 were expressed in all patients and all controls. The genotypes of KIR2DL1, 2DL3, 3DL1, and 2DP1 w... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134562 Fri, 01 Jan 2010 00:00:00 +0100 3134562 http://www.medworm.com/index.php?rid=3134561&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003361%2Fabstract%3Frss%3Dyes In this study, we established a convenient and universal method for detecting MRD in DLBCL. This technique is applicable for over 80% of patients with DLBCL. This could promote systemic MRD studies in the area of DLBCL. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134561 Fri, 01 Jan 2010 00:00:00 +0100 3134561 http://www.medworm.com/index.php?rid=3134560&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609001829%2Fabstract%3Frss%3Dyes Abstract: Real-time quantitative reverse transcriptase polymerase chain reaction method was established for detecting the expression levels of WT1 gene and WT1+17AA isoforms in 226 acute myeloid leukemia (AML) bone marrow (BM) cells. The results showed that WT1 gene was 2–3 logarithms expressed more in AML BM cells at initial diagnosis or relapse than in normal BM cells (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134560 Fri, 01 Jan 2010 00:00:00 +0100 3134560 http://www.medworm.com/index.php?rid=3134559&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002926%2Fabstract%3Frss%3Dyes Abstract: Increased levels of kynurenic acid (KYNA) have been detected in patients with neurological, autoimmune and tumor diseases. The aim of this paper was to determine KYNA levels in the blood and bone marrow plasma of MGUS and MM patients and to find out common events which are characteristic for both pathological stages and correlates with diagnostic markers of MGUS and MM. We also examined whether bone marrow stromal cells (BMSCs) and MM cells could produce KYNA. The levels of KYNA present in plasma and in cell culture media were examined by HPLC.An increased level of KYNA was detected in the blood and marrow plasma of MGUS patients and in the blood plasma of the MM group. In the MM group, the blood KYNA level was the highest in patients with monoclonal IgG protein and with free lig... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134559 Fri, 01 Jan 2010 00:00:00 +0100 3134559 http://www.medworm.com/index.php?rid=3134558&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005001%2Fabstract%3Frss%3Dyes This study evaluates the mRNA expression profile of genes TIMP1, TIMP2, MMP2 and MMP9 in diagnostic bone marrow samples from 134 consecutive ALL children by real-time quantitative PCR. A significant association was observed between higher expression levels of MMP9 and low risk group and absence of extramedullary infiltration and higher expression levels of TIMP2 and MMP2 with T-ALL. TIMP1 gene expression values higher than the median were associated with a significantly lower 5-year event free-survival in univariable (P=0.04) and multivariable analysis (P=0.01). Our data address new information in the complex interaction of the migration/adhesion genes and childhood ALL. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134558 Fri, 01 Jan 2010 00:00:00 +0100 3134558 http://www.medworm.com/index.php?rid=3134557&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003865%2Fabstract%3Frss%3Dyes Abstract: Matrix metalloproteases (MMPs) are endopeptidases involved in tumor cell invasion. Childhood acute lymphoblastic leukemia (ALL) is characterized by its capacity to infiltrate different organs. We analyzed the expression of MMP-2, -9, -14 and TIMP-1 and -2 in a prospective study on 86 children with newly diagnosed ALL (73 B- and 13 T-lineage) and 9 children at relapse with B-ALL. Membrane-bound and intracytoplasmic MMPs and TIMPs were analyzed by flow cytometry, and secreted MMPs were quantified by ELISA. In patients at relapse, MMP-14 was present in a greater proportion of the B-ALL cell population than at diagnosis. In patients with peripheral infiltration, intracytoplasmic MMP-9 was significantly higher than in patients without infiltration. ROC curve and Kaplan–Meier curve a... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134557 Fri, 01 Jan 2010 00:00:00 +0100 3134557 http://www.medworm.com/index.php?rid=3134556&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003701%2Fabstract%3Frss%3Dyes Abstract: Improved treatment of childhood acute lymphoblastic leukemia (ALL) depends on the identification of new molecular markers that are able to predict treatment response and clinical outcome. The development of impaired apoptosis in leukemic cells is one factor that may influence their response to treatment. We investigated the expression of three apoptosis related genes, BCL2L13, CASP8AP2, and Livin, as well as their prognostic significance, in a retrospective study of 90 pediatric ALL patients diagnosed between 1996 and 2007 in Taiwan. Univariant analysis revealed that high expression of BCL2L13 was associated with inferior event-free survival and overall survival (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134556 Fri, 01 Jan 2010 00:00:00 +0100 3134556 http://www.medworm.com/index.php?rid=3134555&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521260900366X%2Fabstract%3Frss%3Dyes Abstract: Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal stem cell (SC) disorders that mainly affect the elderly population. They are characterized by ineffective hematopoiesis which results in quantitative and qualitative cellular defects and high incidence of leukemic transformation. Recent advances in MDS research have led to the development of novel agents which appears to improve remission rates and survival when compared to best supportive care. Currently azacitidine, decitabine, and lenalidomide are approved by the US FDA for the treatment of MDS, while the activity of other novel agents such as histone deacetylase inhibitors, farnesyl-transferase inhibitors, novel thrombopoietic agents, and anti-angiogenesis molecules is under evaluation. Erythropoietin-stimula... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134555 Fri, 01 Jan 2010 00:00:00 +0100 3134555 http://www.medworm.com/index.php?rid=3134554&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609004111%2Fabstract%3Frss%3Dyes Abstract: The term myelodysplastic syndromes (MDS) include a diverse group of diseases in which the bone marrow production of blood cells is disrupted. In spite of the wealth of information on therapeutic options, little is known about the epidemiology of MDS, including population variations and risk factors. A narrative review of published literature and meta-analyses were conducted, identifying and summarizing key reports that describe the association between smoking, alcohol and MDS. There were 10 case–control studies that looked at the association between smoking and MDS, for a total of 1839 cases and 2831 controls. The meta-estimate for the association between ever smoking and MDS was 1.45 (95% CI: 1.21–1.74), with heterogeneity among studies (p=0.05), but no evidence of publicati... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134554 Fri, 01 Jan 2010 00:00:00 +0100 3134554 http://www.medworm.com/index.php?rid=3134553&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609005554%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=3134553 Fri, 01 Jan 2010 00:00:00 +0100 3134553 http://www.medworm.com/index.php?rid=2805831&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609003373%2Fabstract%3Frss%3Dyes Abstract: JAK2 mutation has not been described in patients with chronic lymphocytic leukemia (CLL). We found JAK2 mutation in a patient with CLL and coexisting myeloproliferative neoplasm (MPN). In this patient, we demonstrated the presence of the JAK2 mutation in CD34+ progenitor cells, myeloid lineage cells, megakaryocytes, B lymphocytes but not in T lymphocytes. This case represents the first case report of JAK2 mutation in CLL and may also suggest that, JAK2 mutation most likely represents a secondary event from primary gene mutations involving the primitive stem cells which give rise to MPN and CLL. Furthermore, in this case, we believe that we are the first to demonstrate that JAK2 mutation in myeloid and B lymphoid cells but not T lymphocytes in a case of coexisting CLL and MPN. (So... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=2805831 Fri, 18 Sep 2009 16:36:14 +0100 2805831 http://www.medworm.com/index.php?rid=2805830&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212609002884%2Fabstract%3Frss%3Dyes Abstract: This is the case report of a 47-year-old woman referred to our institution due to acute liver failure related to imatinib, who was submitted to a successful liver transplantation. Nilotinib was safely used post-transplant. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=2805830 Fri, 18 Sep 2009 16:36:14 +0100 2805830