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. Wed, 08 Feb 2012 17:42:09 +0100 http://www.medworm.com/index.php?rid=5610109&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212612000124%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610109 Fri, 20 Jan 2012 22:10:11 +0100 5610109 http://www.medworm.com/index.php?rid=5610124&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005625%2Fabstract%3Frss%3Dyes Abstract: Infections are a major cause of morbidity and mortality in patients with myelodysplastic syndrome (MDS) due to quantitative and qualitative granulocytic defects. We evaluated the in vitro bactericidal and fungicidal activities of neutrophils isolated from MDS. With comparison to those from healthy individuals, MDS neutrophils following infection showed a significantly reduced killing activity against Escherichia coli at 8 (p=0.002), 24 (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610124 Fri, 16 Dec 2011 05:00:00 +0100 5610124 http://www.medworm.com/index.php?rid=5610135&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005315%2Fabstract%3Frss%3Dyes A 62-year old Caucasian woman with a previous history of arterial hypertension, dilative cardiomyopathy and cerebral transient ischemic attack, was admitted to our Department because of marked fatigue, in the absence of fever or hemorrhage. The complete blood count (CBC) revealed pancytopenia, with white blood cell (WBC) count 0.8×109/L in the absence of circulating blasts, hemoglobin (Hb) level 5.4g/dl and platelet (Plt) count 78×109/L, without signs of coagulopathy. Neither hepatomegaly nor splenomegaly were observed on abdominal ultrasonography. The morphological, cytochemical and immunophenotypic analyses performed on peripheral blood and bone marrow aspirate and trephine biopsy documented features consistent with a myelodysplastic syndrome (MDS). Conventional G-banding showed a norm... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610135 Thu, 15 Dec 2011 05:00:00 +0100 5610135 http://www.medworm.com/index.php?rid=5610133&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005327%2Fabstract%3Frss%3Dyes We report an erythroid/myeloid AEL subtype presenting with pulmonary MS, as detected by BALF immunophenotype. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610133 Thu, 15 Dec 2011 05:00:00 +0100 5610133 http://www.medworm.com/index.php?rid=5610120&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005601%2Fabstract%3Frss%3Dyes We report here the outcomes of such nine patients treated at two french institutions by a combination of Rituximab+chemotherapy. We showed that four patients could achieve complete response while four other patients were documented with blast clearance superior to 50% from the baseline in bone marrow. We conclude that our results suggested some efficacy for the use of Rituximab in combination with chemotherapy in the setting of refractory/relapsed adult B-ALL. Larger series within prospective trials are needed to confirm these results. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610120 Thu, 15 Dec 2011 05:00:00 +0100 5610120 http://www.medworm.com/index.php?rid=5495506&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100542X%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495506 Tue, 13 Dec 2011 10:57:24 +0100 5495506 http://www.medworm.com/index.php?rid=5553064&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005261%2Fabstract%3Frss%3Dyes Much has been said and discussed in the last few years, and discussions have increased in frequency during last months, over the need for optimization of prognostic scoring systems in myelodysplastic syndromes . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553064 Mon, 12 Dec 2011 05:00:00 +0100 5553064 http://www.medworm.com/index.php?rid=5610132&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100539X%2Fabstract%3Frss%3Dyes Deletion of the long arm of chromosome 5 is a recurrent cytogenetic abnormality that is frequently found in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The commonly deleted region (CDR) has been identified by various investigators (review in ). The proximal CDR in the 5q31.2 region has been detected in MDS, AML and therapy-related MDS/AML. The distal CDR in the 5q32-q33 region is involved in the pathogenesis of MDS with isolated deletion 5q . Mutational analyses of the residual intact allele have not identified tumor suppressor genes. Haploinsufficiency of multiple genes in the proximal and distal CDRs may cooperate in MDS initiation and/or progression . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610132 Thu, 08 Dec 2011 05:00:00 +0100 5610132 http://www.medworm.com/index.php?rid=5610134&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005297%2Fabstract%3Frss%3Dyes Angiogenesis is recognized as a main feature of many human neoplasms. Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with exerts its biologic effects by interaction with either of 2 high-affinity tyrosine kinase receptors, VEGFR-1 (FLT1) and VEGFR-2 (KDR). Several studies have shown that both monocytes and myeloid precursors are able to produce and secreted VEGF and, commonly, co-express one or both VEGF receptors. On the other hand, overexpression and secretion of VEGF have been observed in 72% of patients with acute myeloid leukemia (AML), with the corresponding mRNA of the genes FLT1 or KDR being expressed in 60% and 19% of AML patients, respectively . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610134 Wed, 07 Dec 2011 05:00:00 +0100 5610134 http://www.medworm.com/index.php?rid=5610123&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005406%2Fabstract%3Frss%3Dyes Abstract: We have utilized the computerized data of a nationwide health plan to elucidate several epidemiologic aspects and risk factor of myelodysplastic syndromes (MDS) in Israel. The annual incidence rate (IR) of reported MDS was of 3.32 per 100,000. Among anemic patients aged 40+, the risk of reported MDS was 56.7 per 100,000. Only 44% of the reported MDS cases had an indication of bone marrow examination. In a multivariable model, older age, hemoglobin level (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610123 Tue, 06 Dec 2011 05:00:00 +0100 5610123 http://www.medworm.com/index.php?rid=5553078&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004292%2Fabstract%3Frss%3Dyes Abstract: p27Kip1 cleavage and caspase-3 regulate cell cycle in human myeloma cells and B cells, however regulation of p27Kip1 cleavage during the cell cycle is not known. In BaF3-FLT3-ITD cells, p27Kip1 undergoes C-terminal cleavage. Inhibition of the PI3K/AKT pathway is associated with decreased cleavage of p27Kip1 and G1 phase arrest. A caspase-3 inhibitor reduces p27Kip1 cleavage and inhibits cell proliferation. Knockdown shRNA against AKT1 reduces cleavage of p27Kip1, inhibits caspase-3 activation, and is associated with a delay in cell cycle progression. Taken together, these findings indicate that AKT1 induces caspase-mediated cleavage of p27Kip1, required for G1-S progression in FLT3-ITD cells. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553078 Tue, 06 Dec 2011 05:00:00 +0100 5553078 http://www.medworm.com/index.php?rid=5610137&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005388%2Fabstract%3Frss%3Dyes Acute myeloid leukemia (AML) is rarely associated with hyperdiploidy. Hyperdiploidy is included under complex karyotype in AML. High hyperdiploidy, i.e. near triploidy and tetraploidy is even rare cytogenetic abnormality seen commonly in elderly male AML patients and is associated with poor prognosis. In the last 3 years we had 5 cases of de-novo AML with near triploidy and tetraploidy. The AML FAB subtypes of these cases included one case of AML-M2 and four cases of AML-M4. Hyperdiploidy was determined by conventional karyotyping. All of our five patients were young and four of them were females. The overall outcome was poor. Because of the rarity of high hyperdiploidy in AML, better understanding of this disease and newer treatment approaches need to be defined. The clinical presentation... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610137 Mon, 05 Dec 2011 05:00:00 +0100 5610137 http://www.medworm.com/index.php?rid=5610126&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005200%2Fabstract%3Frss%3Dyes Abstract: Activation of the mTOR pathway subsequent to phosphatase and tensin homolog (PTEN) mutation may be associated with glucocorticoid (GC) resistance in acute lymphoblastic leukemia (ALL). The combination activity of rapamycin and dexamethasone in cell lines and xenograft models of ALL was determined. Compared with either drug alone, dexamethasone+rapamycin showed significantly greater apoptosis and cell cycle arrest in some cell lines, and was more frequently seen in T-lineage cell lines with PTEN mutation. The combination significantly extended the event-free survival of mice carrying PTEN mutated xenografts. Our data suggest that PI3K/mTOR pathway inhibitors could benefit patients with PTEN mutated T-ALL. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610126 Mon, 05 Dec 2011 05:00:00 +0100 5610126 http://www.medworm.com/index.php?rid=5610112&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005376%2Fabstract%3Frss%3Dyes Abstract: Several new treatments for myelodysplastic syndromes (MDS) have recently become available, or are in development. Patients who could benefit from active treatment must be effectively identified and followed up. Therefore, guidelines for the diagnosis and prognostic evaluation of MDS need to be kept up to date with technological and scientific advances. An expert workshop was convened to review currently available and emerging diagnostic technologies and developments in prognostic classification systems, to ensure appropriate management of individual patients. The panel also provided suggestions to ensure adherence to guidelines and highlighted the mandatory requirement for cytogenetic evaluation in patients with MDS. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610112 Mon, 05 Dec 2011 05:00:00 +0100 5610112 http://www.medworm.com/index.php?rid=5610136&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005303%2Fabstract%3Frss%3Dyes Rarely, acute lymphoblastic leukemia (ALL) can present after a brief preleukemic phase of pancytopenia/bone marrow failure, followed by transient and spontaneous normalization of bone marrow cellularity and peripheral blood counts, with subsequent progression to overt leukemia . These uncommon cases have been well described in children and adolescents, and very rarely in adults, and are often referred to as prodromal ALL or pre-ALL . The pancytopenic episode lasts for a few days up to a few weeks, typically followed by complete and spontaneous recovery . The prognosis has been reported not to be different from patients with classic presentation of ALL . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610136 Fri, 02 Dec 2011 05:00:00 +0100 5610136 http://www.medworm.com/index.php?rid=5610121&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005340%2Fabstract%3Frss%3Dyes Abstract: FLT3 internal tandem duplication (FLT3-ITD) is usually considered as a bad marker for minimal residual disease (MRD) follow-up in acute myeloid leukemia (AML). Our objective was to evaluate the suitability of FLT3-ITD as a target for MRD detection by real-time quantitative PCR, in comparison with two other molecular MRD markers, NPM1 mutation and WT1 overexpression, in 20 adult AML patients treated in Acute Leukemia French Association (ALFA) trials. Overall, these 3 MRD markers showed comparable kinetics in 17/20 (85%) cases. Furthermore, we found that FLT3-ITD MRD levels after induction chemotherapy are predictive of complete remission duration. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610121 Fri, 02 Dec 2011 05:00:00 +0100 5610121 http://www.medworm.com/index.php?rid=5610116&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100525X%2Fabstract%3Frss%3Dyes Abstract: The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610116 Fri, 02 Dec 2011 05:00:00 +0100 5610116 http://www.medworm.com/index.php?rid=5610111&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005352%2Fabstract%3Frss%3Dyes The Bcr-Abl tyrosine kinase inhibitor, imatinib, was introduced into the armamentarium for the treatment of chronic myeloid leukemia (CML) and has revolutionized the management and significantly improved the long term prognosis of the disease. Durable clinical responses are now achievable in a significant number of chronic phase CML patients and their projected survival is expected to be more than 10–15 years . Imatinib is generally well tolerated and many patients can expect to have a normal quality of life. A recent report has also suggested that imatinib can possibly be interrupted safely in patients who have had sustained complete molecular responses . This positive outlook has raised the expectations of many patients in the childbearing age group who may want to parent children. (So... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610111 Fri, 02 Dec 2011 05:00:00 +0100 5610111 http://www.medworm.com/index.php?rid=5553076&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004693%2Fabstract%3Frss%3Dyes We describe 6 patients with HES—1 patient with a newly identified chromosomal abnormality—who received PEG-IFNs. PEG-IFN alpha-2b replaced interferon (IFN) alpha-2b for 4 patients and was initial treatment of 2 patients. PEG-IFN alpha-2a was substituted when PEG-IFN alpha-2b became unavailable. PEG-IFNs were well tolerated and controlled eosinophilia. The dose of PEG-IFNs often could be tapered and the interval between doses lengthened beyond 7days. Adverse effects included dose-related increases in liver enzyme levels, hair loss, mild lymphopenia, and neutropenia. PEG-IFNs are effective treatment of HES. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553076 Mon, 28 Nov 2011 05:00:00 +0100 5553076 http://www.medworm.com/index.php?rid=5553068&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005157%2Fabstract%3Frss%3Dyes Abstract: Background: Disease presentation and outcomes differ by race in a number of malignancies, but data in adult acute myeloid leukemia (AML) are limited.Materials and methods: We conducted a retrospective analysis of pretreatment characteristics, referral and treatment patterns, and outcomes in 548 AML patients evaluated at the University of Maryland Greenebaum Cancer Center, a tertiary care referral center in Baltimore, MD, from 2000 through 2009. Cases were analyzed for time from diagnosis to referral, age, race, gender, socioeconomic status, antecedent hematologic disorder, cytotoxic or radiation therapy for prior malignancy, karyotype, fms-like tyrosine kinase receptor-3 (FLT3) mutations, intensive chemotherapy, clinical trial participation, hematopoietic stem cell transplantatio... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553068 Wed, 23 Nov 2011 05:00:00 +0100 5553068 http://www.medworm.com/index.php?rid=5553065&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005285%2Fabstract%3Frss%3Dyes Approximately 20 years ago, Michael Jackson released the song “Black or White” as the first single from his eighth studio album. The chorus of this song, “it doesn’t matter if you’re black or white”, is a plea for racial tolerance and equality in America. Whether racial and social economic disparities impact the outcome of patients with acute myeloid leukemia (AML) treated in the United States remains controversial . After more than 40 years of systematic clinical research, age and karyotype continue to be the most important prognostic factors in AML . Similar to what has been described in other cancers, some, but not all, previously reported studies suggest that African American patients with AML may have inferior outcomes and may need to be included in the high-risk group . T... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553065 Wed, 23 Nov 2011 05:00:00 +0100 5553065 http://www.medworm.com/index.php?rid=5610117&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004772%2Fabstract%3Frss%3Dyes Abstract: The present study aimed to analyze the expression profile of the microRNAs previously described as associated with childhood ALL, miR-92a, miR-100, miR-125a-5p, miR-128a, miR-181b, miR-196b and let-7e, and their association with biological/prognostic features in 128 consecutive samples of childhood acute lymphoblastic leukemia (ALL) by quantitative real-time PCR. A significant association was observed between higher expression levels of miR-196b and T-ALL, miR-100 and patients with low white blood cell count at diagnosis and t(12;21) positive ALL. These findings suggest a potential activity of these microRNAs in pediatric ALL biology. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610117 Fri, 18 Nov 2011 05:00:00 +0100 5610117 http://www.medworm.com/index.php?rid=5553083&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005030%2Fabstract%3Frss%3Dyes Abstract: MicroRNAs can influence hematopoietic cell lineage commitment and aberrant expression of hematopoietic miRNAs contributes to AML pathology. We found that miR-143 and miR-145 expression is significantly repressed in primary AML patient samples as compared to neutrophils of healthy donors. Further analysis revealed impaired neutrophil differentiation of APL cells upon inhibition of miR-145 expression. Lastly, we identified p73 as transcriptional regulator of miR-143/145 during neutrophil differentiation of APL cells. Our data suggest that low miR-145 levels in APL, possibly due to aberrant expression of p73 transcription factors, contribute to the differentiation block seen in this disease. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553083 Thu, 17 Nov 2011 05:00:00 +0100 5553083 http://www.medworm.com/index.php?rid=5553069&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005145%2Fabstract%3Frss%3Dyes Abstract: Childhood acute lymphoblastic leukaemia is characterized by aberrant proliferation and accumulation of malignant lymphoblasts in bone marrow (BM), followed by their migration into circulation. An enhanced cell-surface expression of ALL-associated 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) was demonstrated. Present investigation reports a positive correlation between the increased density of Neu5,9Ac2-GPs on lymphoblasts and their mobilization from BM involving enhanced Neu5,9Ac2 on CD45 demonstrating modulation of FAK and ERK molecules. In contrast, a small population of cells, identified as haematopoietic precursors, with comparatively lesser Neu5,9Ac2-GPs showed increased binding towards BM stroma. Thus, Neu5,9Ac2-GPs is a developmentally regulated oncofoetal antigen, wh... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553069 Fri, 11 Nov 2011 05:00:00 +0100 5553069 http://www.medworm.com/index.php?rid=5388883&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004917%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388883 Thu, 10 Nov 2011 11:42:22 +0100 5388883 http://www.medworm.com/index.php?rid=5495509&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005078%2Fabstract%3Frss%3Dyes Abstract: For many years there was a widely accepted picture of how a haematopoietic stem cell (HSC) gives rise to the multiple types of blood and immune cells. This described the general nature of stem and progenitor cells and the pathways of cell development. Recent years have seen many attempts to re-draw the map of haematopoiesis. These have become increasingly complex, and they often envisage multiples routes to some cell types. The ‘established’ view that self-renewal in haematopoiesis only occurs in HSCs has been challenged by the recognition of self-renewing HSC-derived progenitor cells that display at least some fate restriction. This evolution of how normal haematopoiesis is viewed has inevitable implications for understanding the origins, disease progression and classificati... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495509 Thu, 10 Nov 2011 05:00:00 +0100 5495509 http://www.medworm.com/index.php?rid=5553063&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005194%2Fabstract%3Frss%3Dyes The use of unrelated umbilical cord blood (UCB) has grown as an allogeneic source of hematopoietic cells for transplantation of patients with hematologic malignancies. EA Boyse and HE Broxmeyer postulated that UCB collected at birth might contain enough hematopoietic stem cells for clinical use. This possibility was strengthened by the knowledge that hematopoietic progenitor cells from UCB could be maintained for many weeks in long-term cultures, suggesting their production from more primitive cells. Since the first CBT performed in 1988 by Dr. Gluckman, more than 20,000 patients have undergone CBT from unrelated CBT donors. Today, approximately 450,000 cord blood grafts are available in 100-cord blood banks . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553063 Wed, 09 Nov 2011 05:00:00 +0100 5553063 http://www.medworm.com/index.php?rid=5495545&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005054%2Fabstract%3Frss%3Dyes Although Philadelphia chromosome (Ph) is most commonly associated with chronic myelogenous leukemia (CML) and precursor B acute lymphoblastic leukemia, in rare instances patients with acute myeloid leukemia (AML) have been reported to be carrying this chromosomal anomaly, with occurrences found to be fewer than 1% of all newly diagnosed AML . Selective BCR-ABL1 tyrosine kinase inhibitors (TKIs) induce a high molecular response rate in patients with CML. TKIs have also been reported to be effective in patients with Ph positive (Ph+) de novo AML, especially in patients undergoing post-remission therapy . While Ph chromosome can also appear in the course of AML, late-appearing Ph+ AML is extremely rare and the efficacy of TKIs in such patients remains unclear. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495545 Wed, 02 Nov 2011 04:00:00 +0100 5495545 http://www.medworm.com/index.php?rid=5553085&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004747%2Fabstract%3Frss%3Dyes Abstract: Following the observation that dopaminergic components are present in normal and malignant B cells, we now provide evidence that they additionally express the functionally related trace amine-associated receptor-1 (TAAR1). Immunodetectable TAAR1 was found in lines derived from a broad range of B-cell malignancy; and in tonsillar B cells, particularly when activated. L3055 Burkitt's lymphoma cells were shown to respond to prototypical TAAR1 agonists in cytotoxicity assays with features of apoptotic death evident; normal B cells were somewhat less sensitive to the agonists. These data raise the possibility that TAAR1 may have therapeutic relevance to leukemia, lymphoma, and wider B-cell pathologies. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553085 Mon, 31 Oct 2011 04:00:00 +0100 5553085 http://www.medworm.com/index.php?rid=5553084&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005042%2Fabstract%3Frss%3Dyes Abstract: BCR-ABL1 kinase-positive leukemia cells accumulate high numbers of DNA double-strand breaks (DSBs) induced by the reactive oxygen species (ROS) or cytotoxic agents. To repair these lesions and prevent apoptosis BCR-ABL1 kinase stimulates the efficiency of DSB repair in leukemia cells. Histone acetylation-dependent chromatin re-modeling plays a crucial role in this process. Here we report that leukemia cells expressing BCR-ABL1 kinase displayed an enhanced histone acetylase activity (HAT) and reduced histone deacetylase activity (HDAC), which was associated with abundant expression of acetylated histones 3 and 4 (Ac-H3 and Ac-H4, respectively). Moreover, Ac-H3 and Ac-H4 readily co-localized with the spontaneous and mitomycin C-induced DSBs in BCR-ABL1-positive leukemia cells sugge... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553084 Mon, 31 Oct 2011 04:00:00 +0100 5553084 http://www.medworm.com/index.php?rid=5495508&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004711%2Fabstract%3Frss%3Dyes Abstract: The early history of leukemia reaches back 200 years. In 1811, Peter Cullen defined a case of splenitis acutus with unexplainable milky blood. Alfred Velpeau defined the leukemia associated symptoms, and observed pus in the blood vessels (1825). Alfred Donné detected a maturation arrest of the white blood cells (1844). John Bennett named the disease leucocythemia, based on the microscopic accumulation of purulent leucocytes (1845). That same year, Rudolf Virchow defined a reversed white and red blood cell balance. He introduced the disease as leukämie in 1847. Henry Fuller performed the first microscopic diagnose of a leukemic patient during life (1846). This gradual process brought us towards our current understanding of this complex disease. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495508 Fri, 28 Oct 2011 04:00:00 +0100 5495508 http://www.medworm.com/index.php?rid=5610131&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611005066%2Fabstract%3Frss%3Dyes We describe here a rare SM-AHNMD associating a systemic mastocytosis and a myeloid neoplasm in blast crisis, with a ZNF198–FGFR1 molecular rearrangement. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610131 Wed, 26 Oct 2011 04:00:00 +0100 5610131 http://www.medworm.com/index.php?rid=5553077&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004735%2Fabstract%3Frss%3Dyes Abstract: We recently reported that Cx43 expression and gap junction intercellular communication (GJIC) between acute leukemic bone marrow stromal cells (BMSCs) were deficient, which could recovery after effective chemotherapy. However, the exact role of GJIC in the hematopoietic microenvironment in leukemic cell death and proliferation is not clear. We show here that following transfection with the Cx43 gene, GJIC function was increased between leukemic BMSCs. Furthermore, compared with leukemic cells alone, the proliferation and apoptosis of leukemic cells co-cultured with BMSCs were inhibited, the percentage of G0-phase cells was higher; and expression of p53 increased and bax decreased. However, after co-culturing leukemic cells with Cx43-modified BMSCs, the number of proliferative and... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553077 Wed, 26 Oct 2011 04:00:00 +0100 5553077 http://www.medworm.com/index.php?rid=5610125&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100470X%2Fabstract%3Frss%3Dyes Abstract: Aberrations in IL-3, GM-CSF and G-CSF induced signaling are frequently reported in acute myeloid leukemia (AML). Herein, we utilized a unique human myeloid leukemic cell line, AML-193, which responds to all three cytokines to analyze the regulation at microRNA level. Using real-time PCR-based miRNA expression profiling, we investigated miRNA signatures regulated by IL-3, GM-CSF and G-CSF for n=704 miRNAs. We discovered that in addition to regulating specific miRNAs, these cytokines also regulate common set of miRNAs, which includes miR-590-5p, miR-219-5p, miR-15b and miR-628-5p. Taken together, we have identified novel candidate miRNAs that may be instructive during leukemic and normal hematopoiesis. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610125 Mon, 24 Oct 2011 04:00:00 +0100 5610125 http://www.medworm.com/index.php?rid=5610113&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004681%2Fabstract%3Frss%3Dyes Abstract: Imatinib should be avoided in women planning to become pregnant or during pregnancy, due to a higher risk of congenital malformations. However, it is not known whether imatinib affects future potential for fertility. Here we analysed ovaries and testes from adult mice receiving imatinib, focusing on testicular and ovarian functions. Seven male and 7 female mice were orally treated with 150mg/kg body weight/day imatinib for two months. No effects on folliculogenesis or spermatogenesis could be observed postmortem by histological examinations, suggesting that, at least in two mouse models of imatinib treatment this tyrosine kinase inhibitor does not reduce fertility. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610113 Mon, 24 Oct 2011 04:00:00 +0100 5610113 http://www.medworm.com/index.php?rid=5610122&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004723%2Fabstract%3Frss%3Dyes Abstract: JAK2V617F allele burden was prospectively measured in untreated patients with polycythaemia vera (PV, n=26) or essential thrombocythaemia (ET, n=36) and compared according to JAK2 46/1 haplotype status. The mean increase in JAK2V617F allele burden per year was 1%, 0.8% and 6% for PV patients with the JAK2 46/1 haplotype in negative, heterozygous and homozygous status, respectively (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610122 Mon, 17 Oct 2011 04:00:00 +0100 5610122 http://www.medworm.com/index.php?rid=5610129&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004577%2Fabstract%3Frss%3Dyes Abstract: The proteasome inhibitor bortezomib (BTZ) is known to be chemotherapeutic in relapsed or refractory mantle cell lymphoma (MCL). Atiprimod (ATI), a novel cationic amphophilic compound, has been tested in clinical trials in multiple myeloma (MM). We sought to evaluate the effect of an ATI–BTZ combination on MCL and to elucidate its therapeutic mechanisms. The ATI and BTZ combination significantly inhibited growth and induced apoptosis of both cultured MCL cell lines and freshly isolated tumor cells from patients with refractory or relapsed MCL. However, the combination yielded lower cytotoxicity in normal peripheral blood mononuclear cells (PBMC). Furthermore, ATI and BTZ induced apoptosis via two different signaling pathways. More significantly, ATI and BTZ markedly delayed tumo... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610129 Fri, 14 Oct 2011 04:00:00 +0100 5610129 http://www.medworm.com/index.php?rid=5610128&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004656%2Fabstract%3Frss%3Dyes Abstract: Survival of acute myeloid leukemia (AML) cells is regulated by their adherence to bone marrow stromal environment. Several adhesion molecules mediate interactions between AML cells and stroma, but their specific role in AML cell survival is still poorly understood. Here, we show that CD44 activation with the Hermes-3 monoclonal antibody enhances primary AML5 blast survival and increases apoptosis resistance of THP-1 monoblastic leukemia cells. Moreover, we show that CD44 activation upregulates the anti-apoptotic Mcl-1 protein and that Mcl-1 is essential for apoptosis resistance of THP-1 cells. These results suggest that Mcl-1 inhibitors might be required to block pro-survival activity of CD44 in AML5. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610128 Thu, 13 Oct 2011 04:00:00 +0100 5610128 http://www.medworm.com/index.php?rid=5610110&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004619%2Fabstract%3Frss%3Dyes Abstract: Cancer treatment has long been based upon cytotoxic therapies that affect all rapidly dividing cells, and as such, is necessarily associated with significant toxicity. More recently, drugs targeted toward pathways critical for tumor cell survival have been developed. With limited off-target activity, such therapies are expected to be better tolerated than broad-acting cytotoxic chemotherapies. BCR-ABL inhibitors in chronic myeloid leukemia are reviewed as a model to investigate the concept of targeted cancer therapies and evaluate how the kinase inhibition profiles of these agents may contribute to their toxicity profiles. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610110 Thu, 13 Oct 2011 04:00:00 +0100 5610110 http://www.medworm.com/index.php?rid=5495544&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100467X%2Fabstract%3Frss%3Dyes We report a patient with prolonged pyrexia secondary to azacytidine-induced interstitial pneumonitis which was being managed as neutropenic sepsis with minimal response to multiple antimicrobial therapies. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495544 Thu, 13 Oct 2011 04:00:00 +0100 5495544 http://www.medworm.com/index.php?rid=5495539&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004620%2Fabstract%3Frss%3Dyes Chronic myeloid leukemia (CML) is characterized by triphasic course. Overall survival of patients with CML is usually determined by the duration of the chronic phase prior to blast crisis. The duration of the chronic phase generally exceeds 10 years for the patients who did not suffer from the blastic phase earlier. The longest duration was 29 years according to the literature . However, the blastic phase is generally refractory to the therapy. To the best of our knowledge, there are neither any reported case with long-term survival of the CML-blastic phase (CML-BP) without stem cell transplantation nor any clinical study regarding CML-BP with more than 10 years of follow-up. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495539 Thu, 13 Oct 2011 04:00:00 +0100 5495539 http://www.medworm.com/index.php?rid=5495538&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004632%2Fabstract%3Frss%3Dyes We report a novel MYC translocation in a single case involving chromosome band 12p12. Using chromosome walking – fluorescent in situ hybridization (FISH) based analysis we have identified the candidate partner gene at translocation site and mapped the corresponding breakpoint near MYC on chromosome band 8q24. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495538 Thu, 13 Oct 2011 04:00:00 +0100 5495538 http://www.medworm.com/index.php?rid=5495530&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004668%2Fabstract%3Frss%3Dyes The objective of this report is to describe a case of a patient with a FLT3-ITD positive, refractory acute erythroid leukemia with t(X;9;6), who responded dramatically to sorafenib and achieved a long-term remission following an allogeneic stem cell transplantation (allo-SCT). (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495530 Thu, 13 Oct 2011 04:00:00 +0100 5495530 http://www.medworm.com/index.php?rid=5495527&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004565%2Fabstract%3Frss%3Dyes Abstract: Krüppel-like factor 5 (KLF5) has been implicated as a tumor suppressor in various solid tumors such as breast and prostate, and recent studies have demonstrated a role for this protein in neutrophil differentiation of acute promyelocytic leukemia cells in response to ATRA. Here, we show that KLF5 expression increases during primary granulocyte differentiation and that expression of KLF5 is a requirement for granulocyte differentiation of 32D cells. In AML, we show that KLF5 mRNA expression levels are reduced in multiple French–American–British subtypes compared to normal controls, and also in leukemic stem cells relative to normal hematopoietic stem cells. We demonstrate that in selected AML cases, reduced expression is associated with hypermethylation of the KLF5 locus in t... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495527 Thu, 13 Oct 2011 04:00:00 +0100 5495527 http://www.medworm.com/index.php?rid=5305192&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100436X%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305192 Wed, 12 Oct 2011 09:41:35 +0100 5305192 http://www.medworm.com/index.php?rid=5553080&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004553%2Fabstract%3Frss%3Dyes This study investigates the dynamic regulation of human hematopoietic cell kinase (HCK) in acute promyelocytic leukemia (APL) and the underlying molecular mechanisms. First, the level of HCK in APL blasts was found lower than that in normal granulocytes and monocytes. Second, the HCK promoter was repressed by PML/RARα and this repression required PU.1. PU.1 was capable of transactivating the HCK promoter through a region encompassing three PU.1 motifs. Chromatin immunoprecipitation assays provided evidence that PU.1 and PML/RARα bound to the HCK promoter in vivo. Finally, we found an unequivocal increase of HCK expression upon treatment with all-trans retinoic acid. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553080 Wed, 12 Oct 2011 04:00:00 +0100 5553080 http://www.medworm.com/index.php?rid=5495542&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004607%2Fabstract%3Frss%3Dyes Multiple myeloma (MM) is characterized by clonal proliferation of plasma cells in the bone marrow. Extramedullary plasmacytomas (EMP) can occur either at initial diagnosis of MM or later during the course of the disease. EMP can affect any area of tissue, but the pleura, lymph nodes, soft tissue, liver, skin, lungs, central nervous system, genitourinary system, breast and pancreas are more frequently involved. The presence of EMP in MM is associated with aggressive disease leading to shorter overall survival and progression-free survival . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495542 Wed, 12 Oct 2011 04:00:00 +0100 5495542 http://www.medworm.com/index.php?rid=5553070&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004243%2Fabstract%3Frss%3Dyes Abstract: We treated 37 patients with polycythemia vera with imatinib mesylate (IM). The overall response rate was 49%. Thirty percent had a complete response, and 19%, a partial response. Thirty-one patients were treated for >120days. Frequent side effects included nausea, diarrhea, edema, and skin rash. Whereas IM was effective in controlling erythropoiesis and reducing spleen size it was ineffective in controlling thrombocytosis. Normocellular marrow developed in 4 patients who had a complete response. Progression to overt myelofibrosis occurred in 3. Nevertheless, 6 patients have had a sustained complete response while on IM for >6years. These patients were young, had high phlebotomy requirements, and only slightly elevated platelet counts. Therefore, we believe there may be a role for... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553070 Mon, 10 Oct 2011 04:00:00 +0100 5553070 http://www.medworm.com/index.php?rid=5495541&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004279%2Fabstract%3Frss%3Dyes Jumping translocations (JTs) are rare chromosome rearrangements characterized by the relocalization of the same part of a donor chromosome to more than one recipient chromosome. To date, fewer than 70 JTs have been reported in hematological malignancies and solid tumors . Only 18 JTs have been described in myeloid-lineage hematological disorders. Of these, 5 involve the long arm of a chromosome 3 (3q) JTs with gain of a chromosome 8 (trisomy 8) . Among these, 2 had acute myeloid leukemia (AML)-M5b, 1 had AML-M5a, 1 had an unspecified myeloproliferative neoplasm (MPN(u)), and 1 had jCMML→unspecified AML . Here, we describe the 6th 3q JT case with trisomy 8 in a patient with AML-M5. But notably it is the first case with quantitative FISH analyses (Q-FISH) of telomere lengths in normal and ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495541 Mon, 10 Oct 2011 04:00:00 +0100 5495541 http://www.medworm.com/index.php?rid=5553066&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004590%2Fabstract%3Frss%3Dyes We report the results of unrelated cord blood transplantation (CBT) after myeloablative conditioning regimen in 16 patients with hematologic malignancies from 15 to 20 years old. The median times of myeloid and platelet engraftment were 21 and 38 days, respectively. The cumulative incidences of acute graft-vs-host disease (GVHD) was 62.0%, all of which were grade I or II, and that of extensive-type chronic GVHD was 12.5%. The probabilities of overall and disease-free survival at 3 years were 68.2% and 48.6%, respectively, comparable to adult or childhood cases. Adolescents and young adult patients with hematologic malignancies who have no HLA-matched adult donors could be considered as candidates for CBT. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553066 Fri, 07 Oct 2011 04:00:00 +0100 5553066 http://www.medworm.com/index.php?rid=5495536&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004644%2Fabstract%3Frss%3Dyes Primary immunodeficiencies are well recognized conditions associated with an increased risk of cancer. Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by defective immunity, severe pre- and postnatal retarded growth and sun-sensitive facial erythema . Malignant neoplasms have been detected in 50% of patients recorded in the Bloom's Syndrome Registry (BSR) [http://weill.cornell.edu/bsr] and, although the distribution of tumor types resembles that in the general population, they occur more frequently and at much earlier ages in BS . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495536 Fri, 07 Oct 2011 04:00:00 +0100 5495536 http://www.medworm.com/index.php?rid=5495514&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003778%2Fabstract%3Frss%3Dyes Abstract: The prognostic relevance of 12p deletion is controversial in multiple myeloma (MM) and the status of 12p deletion is unknown in other plasma cell disorders. We investigated 12p deletion in 88 patients with MM, 19 patients with monoclonal gammopathy of undetermined significance (MGUS), and 17 patients with plasma cell leukemia (PCL). Cytoplasmic immunoglobulin light chain immunofluorescence with simultaneous FISH analysis (cIg-FISH) detected hemizygous 12p deletion in 8% of MM and 24% of PCL, respectively, but in none of the MGUS cases (p=0.0366). 12p deletions were found in 5 of 7 (71%) MM patients at diagnosis with stage III disease (Durie–Salmon), 2 of 7 (28%) with stage I or II. Of 11 cases with 12p deletions, 6 (55%) had coexistence of p53 deletions, including 3 of 7 (42%) ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495514 Fri, 07 Oct 2011 04:00:00 +0100 5495514 http://www.medworm.com/index.php?rid=5553079&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004346%2Fabstract%3Frss%3Dyes Abstract: Bortezomib is a proteasome inhibitor important to the therapy of multiple myeloma (MM), though a number of patients show resistance to this drug. To study the cellular basis of this resistance we have generated a MM cell line displaying enhanced (5–6-fold) resistance to bortezomib by serial cultivation of RPMI 8226 cells with increasing concentrations of this drug. Bortezomib-resistant cells (8226/7B) became bigger in size than parental cells and nearly doubled the amount of DNA per cell, evolving from hypotriploidy to near-tetraploidy. 8226/7B displayed lowered Noxa accumulation and reduced caspase-3 activation in response to bortezomib. Resistant 8226/7B cells overexpressed the PSMβ5 proteasome subunit, the molecular target of bortezomib, both at the mRNA and protein level. ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553079 Wed, 05 Oct 2011 04:00:00 +0100 5553079 http://www.medworm.com/index.php?rid=5553072&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004176%2Fabstract%3Frss%3Dyes In this study, we analyzed NRP-1 expression level in 40 acute leukemia patients [20 acute myeloid leukemia (AML) and 20 acute lymphoblastic leukemia (ALL)] and 10 healthy controls using Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RTQ-PCR) aiming to show Neuropilin-1 (NRP-1) gene expression pattern in acute leukemia patients and its role in disease severity and progression. NRP-1 was expressed in 80% and 95% of ALL and AML respectively with levels higher in patients than controls and in ALL than AML patients. NRP-1 levels were significantly correlated with blast percentage and complete remission. We conclude that NRP-1 is significantly associated with acute leukemia and that its level might serve as an indicator for disease severity and progression. NRP-1 signali... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553072 Wed, 05 Oct 2011 04:00:00 +0100 5553072 http://www.medworm.com/index.php?rid=5495516&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004152%2Fabstract%3Frss%3Dyes This study was designed to evaluate the antileukemic effect of clomiphene in patients with AML. Eleven patients with recurrent or chemoresistant AML aged 54–79 years received oral clomiphene (25–50mg per day), for seven consecutive days per cycle, up to three cycles while concurrent non intravenous chemotherapy was continued. Ten patients showed a partial response or remained stable during therapy; 7 had a rapid increase in disease parameters shortly after cessation of therapy while four patients survived 6–18 months. We believe that clomiphene contributes to stabilizing disease during therapy and appears to prolong survival in a subset of relapsed or refractory patients and may perhaps be considered as a new therapeutic option. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495516 Wed, 05 Oct 2011 04:00:00 +0100 5495516 http://www.medworm.com/index.php?rid=5495513&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004322%2Fabstract%3Frss%3Dyes Abstract: We speculated that some individuals with de novo acute myelogenous leukemia (AML) may have undiagnosed Fanconi Anemia (FA). Data from patients enrolled on AML protocol CCG-2961, published FA cohort studies, SEER, and Bayes rule were used to estimate the probability of FA among all newly diagnosed AML cases, and among those who had no or delayed recovery of the absolute neutrophil count following initial chemotherapy. We determined that the probability of undiagnosed FA in patients in a treatment trial for newly diagnosed patients was around 0.18%, and around 0.83% in the subset who had poor marrow recovery. We suggest that FA or other inherited bone marrow failure syndromes be considered prior to treatment, or certainly among those with poor recovery. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495513 Wed, 05 Oct 2011 04:00:00 +0100 5495513 http://www.medworm.com/index.php?rid=5495512&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004334%2Fabstract%3Frss%3Dyes Recurrent or refractory AML is frequent and still associated with a poor prognosis with less than 10% long-term survival without allogeneic transplantation . Depending on prognostic subgroups 10–50% of patients with newly diagnosed AML may not achieve a complete remission having a primary refractory disease. Salvage therapies produce CR rates from 10 to 60% depending on therapeutic regimen and duration of first CR . AML of the elderly independently from other prognostic factors is associated with a devastating survival of partially less than 4 months . That is only in part caused by age related comorbidity and enhanced chemotoxicity . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495512 Wed, 05 Oct 2011 04:00:00 +0100 5495512 http://www.medworm.com/index.php?rid=5553067&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004309%2Fabstract%3Frss%3Dyes Conclusions: The development and comparison of prognostic systems have to take into account their stability versus the possibility or need for re-evaluation. Possibly not only re-evaluation after time is of importance, but also different weighting of items constituting scores. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553067 Tue, 04 Oct 2011 04:00:00 +0100 5553067 http://www.medworm.com/index.php?rid=5553086&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004310%2Fabstract%3Frss%3Dyes Aplastic anemia (AA) is defined as a pancytopenia associated with unexplained bone marrow hypocellularity. The incidence of acquired AA in the Western hemisphere is around 2 new cases per million inhabitants per year . Age distribution shows peaks in children and young adults and in patients aged >60 years. Patients with AA commonly present with anemia, skin or mucosal hemorrhages and, less frequently, with infection. Acquired AA can be considered in most cases as a T cell-mediated autoimmune disorder, targeted against the hematopoietic progenitors, leading to bone marrow failure . Viral infections, drugs, exposure to chemicals, pregnancy, or unknown agents seem to trigger autoimmunity in patients with predisposition. Associations of AA with other autoimmune diseases have been shown in a r... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553086 Mon, 03 Oct 2011 04:00:00 +0100 5553086 http://www.medworm.com/index.php?rid=5495540&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004267%2Fabstract%3Frss%3Dyes Rearrangements of the mixed lineage leukemia (MLL) locus at 11q23 are associated with the development of acute myeloid leukemias (AML) and acute lymphoblastic leukemias (ALL), characterized by more than 20% of blast cells. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495540 Mon, 03 Oct 2011 04:00:00 +0100 5495540 http://www.medworm.com/index.php?rid=5495533&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004255%2Fabstract%3Frss%3Dyes The outcome of Philadelphia-positive chronic myeloid leukemia (Ph+ CML) has been dramatically improved by the introduction of imatinib (IM), a highly specific tyrosine-kinase inhibitor (TKI). The recent update of the IRIS trial showed an 85% estimated overall survival at 8 years with imatinib . Despite these excellent results, according to the European LeukemiaNet or NCCN definitions for response evaluation 20–30% of the patients fail IM therapy , and in approximately 40–50% of resistant patients one or more BCR-ABL kinase domain point mutations are detected. Second generation TKI nilotinib (NIL) and dasatinib (DAS) may induce cytogenetic and molecular responses in CML patients resistant to IM and are approved for second-line treatment. In some resistant patients, the mutational status... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495533 Mon, 03 Oct 2011 04:00:00 +0100 5495533 http://www.medworm.com/index.php?rid=5610119&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004024%2Fabstract%3Frss%3Dyes We describe five cases, with a diminished ATM FISH signal, investigated by TP53 mutation/dysfunction studies and single nucleotide polymorphism (SNP) array. The diminished signal represented loss of the ATM gene, which could have been missed were the cases not further investigated. These rare cases highlight the need for careful consideration of the choice of probe and interpretation of unusual signal patterns in FISH screening. We define a new minimal region of deletion at 11q22.3. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610119 Wed, 28 Sep 2011 04:00:00 +0100 5610119 http://www.medworm.com/index.php?rid=5495529&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004231%2Fabstract%3Frss%3Dyes In a recent issue of Leukemia Research, Lopotová et al. suggest the existence of a reciprocal regulatory loop between BCR-ABL and microRNA-451 (miR-451) as a maintenance mechanism of the leukemic state of CML cells. The authors also report that down regulation of miR-451 might be inversely related to BCR-ABL kinase activity in chronic myeloid leukemia (CML) cells. MiRNAs are non-coding RNAs of 21–25 nucleotides that have been implicated in a number of biological processes, regulating gene expression by promoting mRNA degradation or repressing its translation. Aberrant miRNA expression has been described for a variety of solid tumors and hematological malignancies, including CML. Some miRNAs, as for example miR-150, miR-151, miR-10a and miR-96 were seen aberrantly expressed in purified C... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495529 Mon, 26 Sep 2011 04:00:00 +0100 5495529 http://www.medworm.com/index.php?rid=5495526&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003304%2Fabstract%3Frss%3Dyes Abstract: In AML, prevention of GvHD leads to better tolerance of myeloablative therapy. 66 individuals with AML in CR underwent myeloablative conditioning and transplantation with allogeneic PBPC grafts. Median presentation age was 44.5 years. Karyotyping was intermediate in 48% and of unfavourable risk in 36%. For GvHD prophylaxis, PBPC harvests were incubated ex vivo with anti CD52 antibodies. TRM at day 100 and 1 year was 9% and 17%. At a median of 1018 days 65% are alive. Grade >1 GvHD was seen in 11%. GvHD and adverse karyotype were associated with treatment failure. In younger patients preservation of the dose intensity may improve cure rates. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495526 Wed, 21 Sep 2011 04:00:00 +0100 5495526 http://www.medworm.com/index.php?rid=5610130&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100419X%2Fabstract%3Frss%3Dyes Abstract: Lack of suitable mouse models for central nervous system (CNS)-associated leukemias has hindered mechanism-guided development of therapeutics. By transplanting retrovirus-transformed mouse erythroleukemia cells into syngeneic mice, we developed a new animal model of meningeal leukemia associated with rapid paralysis. Necropsy revealed massive proliferation of the leukemic cells in the bone marrow (BM) followed by pathological angiogenesis and invasion of the leukemic cells into the meninges of the CNS. Further analysis demonstrated that the erythroleukemia cells secreted high levels of VEGF and preferentially adhered in vitro to fibronectin. This unique animal model for meningeal leukemia should facilitate studies of engraftment and proliferation of leukemic cells in the BM and t... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610130 Mon, 19 Sep 2011 04:00:00 +0100 5610130 http://www.medworm.com/index.php?rid=5495525&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100422X%2Fabstract%3Frss%3Dyes Abstract: In a Phase I/II clinical trial, 13 higher risk red blood cell-dependent myelodysplastic syndrome (MDS) patients unresponsive to hypomethylating therapy were treated with the multikinase inhibitor ON 01910.Na. Responses occurred in all morphologic, prognostic risk and cytogenetic subgroups, including four patients with marrow complete responses among eight with stable disease, associated with good drug tolerance. In a subset of patients, a novel nanoscale immunoassay showed substantially decreased AKT2 phosphorylation in CD34+ marrow cells from patients responding to therapy but not those who progressed on therapy. These data demonstrate encouraging efficacy and drug tolerance with ON 01910.Na treatment of higher risk MDS patients. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495525 Mon, 19 Sep 2011 04:00:00 +0100 5495525 http://www.medworm.com/index.php?rid=5495510&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004206%2Fabstract%3Frss%3Dyes Almost all patients with plasma cell myeloma harbour chromosomal aberrations. Due to the clinical heterogeneity of patients with plasma cell myeloma with survival times ranging from some weeks to more than one decade, there has lately been much emphasis on the characterization of such genetic lesions in order to define their pathogenetic role as well as their prognostic value in this entity. Whereas IGH translocations were suggested to represent primary genetic lesions with some of them constituting an adverse risk factor, like t(4;14)(p16;q32), genetic events such as TP53 deletions or abnormalities of chromosome 1p or 1q were discussed to be secondary lesions, occurring during myeloma progression . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495510 Mon, 19 Sep 2011 04:00:00 +0100 5495510 http://www.medworm.com/index.php?rid=5610114&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100405X%2Fabstract%3Frss%3Dyes This study firstly compared dynamic change of Fas/Fas ligand (FasL) system in plasma and also in the surface of endothelial cell microparticles (EMPs) in aGVHD patients, pre-aGVHD patients (7, 14, 21 and 28 days after transplantation), non-aGVHD patients and normal controls. Plasma soluble FasL (sFasL) was detected by ELISA. Fas, FasL and EMPs were evaluated by Confocal microscopy and flow cytometric analysis respectively. Significantly higher levels of sFasL and EMPs were detected in the patients at the time of aGVHD attack. In addition, sFasL exhibited significant elevation but EMPs exhibited simultaneously decrease within the early phase (+21d) after allo-HSCT in pre-aGVHD group compared with non-aGVHD group. At +21d, there was a significant difference of sFasL and EMPs between pre-aGVH... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610114 Thu, 15 Sep 2011 04:00:00 +0100 5610114 http://www.medworm.com/index.php?rid=5553071&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004218%2Fabstract%3Frss%3Dyes Abstract: We performed quantitative and qualitative analyses of conventional cytogenetic analysis and interphase FISH results in 87 MDS patients. The quantity of clonal cells for each chromosome of CCA did not correlate with the result of iFISH (r, range 0.0761–1.0577). The clonal cell percentage in CCA was higher in patients with >5% bone marrow blasts than those with (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553071 Thu, 15 Sep 2011 04:00:00 +0100 5553071 http://www.medworm.com/index.php?rid=5495515&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004048%2Fabstract%3Frss%3Dyes Abstract: We investigated TET2 deletion in 418 patients with hematological malignancies. Overall interphase FISH detected complete or partial TET2 monoallelic deletion (TET2del) in 20/418 cases (4.7%). TET2del was very rare in lymphoid malignancies (1/242 cases; 0.4%). Among 19 positive myeloid malignancies TET2del was associated with a 4q24 karyotypic abnormality in 18 cases. In AML, TET2del occurred in CD34-positive hematopoietic precursors and preceded established genomic abnormalities, such as 5q− and −7/7q−, which were the most frequent associated changes (Fisher's exact test P=0.000). (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495515 Thu, 15 Sep 2011 04:00:00 +0100 5495515 http://www.medworm.com/index.php?rid=5495507&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004164%2Fabstract%3Frss%3Dyes Abstract: It is now generally appreciated that hematologic neoplasms can develop over many years if not decades, often being initially occult or showing minimal (subdiagnostic) abnormalities. However, whereas such early neoplastic conditions have been defined in some detail in lymphoproliferative neoplasms, little is known about minimal lesions preceding the manifestation of an overt myeloid neoplasm, about underlying mechanisms, the clinical course and outcome, and the prognostic significance of such conditions. Members of several groups have recently described two ‘premalignant’ myeloid conditions, namely idiopathic cytopenia of undetermined significance (ICUS) and idiopathic bone marrow dysplasia of uncertain significance (IDUS). At least in some patients these are neoplastic condit... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495507 Thu, 15 Sep 2011 04:00:00 +0100 5495507 http://www.medworm.com/index.php?rid=5495511&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004188%2Fabstract%3Frss%3Dyes TET2 is an Fe(II)- and alpha-ketoglutarate dependent enzyme known to be affected by loss-of-function mutations in myeloid malignancies . Recently all TET family members including TET2 were shown to catalyze the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, or 5-carboxylcytosine . It is currently believed that these enzymatic modifications of methylcytosines are an important step in the active demethylation of DNA . Biologically, it has very recently been demonstrated that in vivo loss of TET2 is associated with a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo. Furthermore, TET2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation in mice . (Source: Leukemia Research... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495511 Wed, 14 Sep 2011 04:00:00 +0100 5495511 http://www.medworm.com/index.php?rid=5553075&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004140%2Fabstract%3Frss%3Dyes Abstract: A meta-analysis was performed to demonstrate the prognostic significance of FLT3-TKD mutations in acute myeloid leukemia (AML). The overall hazard ratio (HR) of FLT3-TKD/FLT3-wild type (WT) for disease-free survival (DFS) was 1.20. The overall HRs for overall survival (OS) of FLT3-TKD to FLT3-ITD and FLT3-WT were 0.87 and 1.18. For non-promyelocytic AML with intermediate cytogenetics, the overall HR for DFS of FLT3-TKD/FLT3-ITD was 0.71. The HR for OS of FLT3-TKD/FLT3-ITD was 0.75. Adult AML patients with FLT3-TKD mutations exhibit better outcomes than those with FLT3-ITD. The patients with FLT3-TKD mutations with intermediate cytogenetics had similar OS as those with FLT-WT mutations. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553075 Mon, 12 Sep 2011 04:00:00 +0100 5553075 http://www.medworm.com/index.php?rid=5495535&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004103%2Fabstract%3Frss%3Dyes Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hemopoietic disorders associated with bone marrow (BM) failure, peripheral cytopenias, and an increased risk of developing acute myeloid leukemia (AML) . In a recent phase III trial, the hypomethylating agent azacitidine (Vidaza®, Celgene Corporation, Summit, NJ) prolonged overall survival (OS) versus conventional care regimens (CCR; 24.5 vs 15.0 months, respectively; p=0.0001) in patients with intermediate(int)-2-/high-risk MDS or World Health Organization (WHO)-defined AML with low blast count(20–30% bone marrow [BM] blasts) . Additionally, azacitidine has been shown to delay disease progression, increase red blood cell (RBC) transfusion independence and enhance quality of life compared with supportive care in patient... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495535 Mon, 12 Sep 2011 04:00:00 +0100 5495535 http://www.medworm.com/index.php?rid=5610127&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003742%2Fabstract%3Frss%3Dyes Abstract: Nasal NK/T-cell lymphoma (NKTL) is a highly aggressive disease. Although radiotherapy is the first-line of treatment for NKTL, the clinical outcome is poor. Thus, there is a need for an effective radiosensitizer to improve the survival rate of patients. NF-κB activation contributes to cell survival as well as chemo- and radio-resistance in various cancer cells. In NKTL, the constitutive activation of NF-κB is also a critical factor. In the present study, we used two EBV-expressing NKTL cell lines (Hank-1 and NK-92) to evaluate the radiosensitizing effect of methotrexate (MTX), highlighting the role of NF-κB. Combined treatment of MTX and IR significantly induced apoptosis and growth inhibition in both NKTL cells. The synergistic cytotoxicity was correlated with blocking nuclea... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610127 Wed, 07 Sep 2011 04:00:00 +0100 5610127 http://www.medworm.com/index.php?rid=5495543&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004127%2Fabstract%3Frss%3Dyes Precursor B-cell lymphoblastic lymphoma (B-LBL) is uncommon and rarely presents as a primary solitary bone tumor. Precursor B-cell neoplasms usually originate in bone marrow as B-cell acute lymphoblastic leukemia and, in advanced stages, can produce destructive bone lesions. Several cases are reported in the literature describing B-LBL manifesting as a solitary bone tumor . However B-LBL with oral cavity involvement is extremely rare. Here we present the case of a childhood B-LBL in the mandible. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495543 Wed, 07 Sep 2011 04:00:00 +0100 5495543 http://www.medworm.com/index.php?rid=5495537&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004115%2Fabstract%3Frss%3Dyes The incorporation of the tyrosine kinase inhibitor imatinib mesylate for frontline treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph-positive ALL) has significantly improved the antileukemic efficacy of induction therapy. Several ALL study groups have demonstrated complete remission rates above 90% in patients undergoing imatinib-containing therapeutic regimens and improved long-term outcome in these patients . Despite such improvement, however, relapse does occur largely due to acquisition of imatinib resistance . Although numerous point mutations in the ABL kinase domain that impair imatinib binding have been identified as a major mechanism of acquired resistance in CML patients, similar data on Ph-positive ALL patients are limited . Here, we describe a case in which a ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495537 Wed, 07 Sep 2011 04:00:00 +0100 5495537 http://www.medworm.com/index.php?rid=5388893&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004061%2Fabstract%3Frss%3Dyes Abstract: Insulin-like growth factor (IGF) signaling plays an important role in many tumors and overexpression of IGF Binding Protein (IGFBP) 2 has been associated with adverse outcome in childhood leukemia. Here, we evaluated IGFBP2 mRNA expression and its prognostic implications in 99 adult acute myeloid leukemia (AML) patients by quantitative real-time RT-PCR. High IGFBP2 was associated with a high incidence of primary resistant disease (IGFBP2 high 65%, IGFBP2 low 32%; P=0.02) and was independently predictive for therapy resistance [OR 3.6 (95% CI 1.2–11); P=0.02] in multivariate analyses. Gene-expression profiling revealed an up-regulation of genes implicated in leukemogenesis (MYB, MEIS1, HOXB3, HOXA9) and genes associated with adverse outcome (ERG, WT1) in patients with high IGFBP... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388893 Wed, 07 Sep 2011 04:00:00 +0100 5388893 http://www.medworm.com/index.php?rid=5305193&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003705%2Fabstract%3Frss%3Dyes Abstract: This paper speculates on the role of infection in modifying a young child's risk of promoting precursor B-cell acute lymphoblastic leukemia (ALL). It is suggested that the heat shock instigated by infections, particularly in infancy, stimulates Th1 pro-inflammatory cytokines and an apoptosis-inhibitory environment. This infective stress also increases the number of cooperating oncogenic mutations in pre-leukemic cells, especially if the primary adaptive immune response is delayed. The glucocorticoid release that follows leads to acute thymic involution, a decline in antitumor immunity, and maturation arrest of B-lymphocytes. The infective lymphoid recovery hypothesis addresses an apparent contradiction–that a non-hygienic environment primes the adaptive immune response and is p... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305193 Wed, 07 Sep 2011 04:00:00 +0100 5305193 http://www.medworm.com/index.php?rid=5610118&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003900%2Fabstract%3Frss%3Dyes Abstract: The cure rate for pediatric patients with B precursor acute lymphoblastic leukemia (pre-B ALL) is steadily improving, however relapses do occur despite initial response to therapy. To identify links between drug resistance and gene deregulation we used oligonucleotide microarray technology and determined in 184 pre-B ALL specimen genes differentially expressed compared to normal CD34+ specimens. We identified 20 signature genes including CTGF, BMP-2, CXCR4 and IL7R, documented to regulate interactions in the bone marrow. We recorded remarkably similar levels of expression in three independent patient cohorts, and found distinct patterns in cytogenetically defined subgroups of pre-B ALL. The canonical pathways that were affected are involved in inter- and intra-cellular communicat... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610118 Mon, 05 Sep 2011 04:00:00 +0100 5610118 http://www.medworm.com/index.php?rid=5495532&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004085%2Fabstract%3Frss%3Dyes The germline constitutive JAK2 haplotype, called GGCC or 46/1, is a susceptibility factor for BCR-ABL negative classic myeloproliferative neoplasms (MPNs), . The mechanisms linking the haplotype block and the acquired MPN remain unclear. Two hypotheses have been proposed: the “hypermutability” of the chromosome region that could facilitate the arising of typical MPN somatic mutations , or the “fertile ground hypothesis” that could confer selective advantage to cells carrying the 46/1 haplotype . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495532 Mon, 05 Sep 2011 04:00:00 +0100 5495532 http://www.medworm.com/index.php?rid=5495531&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004073%2Fabstract%3Frss%3Dyes Dasatinib is a potent inhibitor of tyrosine-kinases (TKI), such as BCR-ABL, PDGFR-β, c-kit, and of SRC-family kinases. It is indicated for treatment of Chronic Myeloid Leukaemia (CML) and Ph-positive Acute Lymphoblastic Leukaemia after imatinib failure/intolerance, and has recently obtained authorisation as first-line therapy in CML, based on results in newly diagnosed patients with chronic phase CML . At the previously recommended dose of 70mg BID, the most relevant non-haematological side effect of dasatinib therapy was exudative pleural effusion (PE), which has been observed in up to 14–35% of patients , and has been related to an autoimmune-mediated mechanism or inhibition of PDGFR-β, as opposed to fluid retention. The occurrence of grade 3–4 PE, however, has decreased to less th... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495531 Mon, 05 Sep 2011 04:00:00 +0100 5495531 http://www.medworm.com/index.php?rid=5495522&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003808%2Fabstract%3Frss%3Dyes Abstract: The diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) can be challenging, owing to the absence of traditional lineage-specific markers, but is facilitated by CD4/CD56 co-expression and frequent skin involvement. Herein, we present our collective experiences with three BPDCN cases lacking cutaneous presentation and the inherent diagnostic pitfalls. Taken in context of similar historical cases, we suggest that BPDCN with “leukemic” presentation (L-BPDCN) otherwise presents no major distinguishing features and is at least as aggressive as its cutaneous-involved BPDCN counterpart. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495522 Mon, 05 Sep 2011 04:00:00 +0100 5495522 http://www.medworm.com/index.php?rid=5495534&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004097%2Fabstract%3Frss%3Dyes Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by peripheral cytopenias due to ineffective hematopoiesis and an increased risk of developing acute leukemia. The identification of chromosomal abnormalities by conventional cytogenetics is crucial to determine prognosis and therapeutic approach . Nevertheless, a large proportion of MDS patients (40–65%) present normal karyotype at diagnosis . Although chromosome banding analysis is the gold standard technique, some investigators advocate that the frequency of abnormalities is underestimated using conventional techniques because of low- proliferating aberrant clones reduce the probability of detection. Therefore, a lot of studies have focused on evaluating the potential role of interphase fluorescen... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495534 Fri, 02 Sep 2011 04:00:00 +0100 5495534 http://www.medworm.com/index.php?rid=5305215&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100381X%2Fabstract%3Frss%3Dyes Abstract: Recent studies have shown that SNPs mapping to 7p12.2 (IKZF1), 9p21 (CDKN2A), 10q21.2 (ARID5B), and 14q11.2 (CEBPE) and carrier status for recessively inherited Nijmegen Breakage syndrome (NBS) influence childhood acute lymphoblastic leukemia (ALL) risk. To examine these relationship, we analysed 398 ALL cases and 731 controls from Poland. Statistically significant association between genotype at 7p12.2 (IKZF1), 10q21.2 (ARID5B) and the NBS associated locus, 8q21.3 (NBN) and ALL risk was found; odds ratios (ORs), 1.34 (P=0.002), 1.33 (P=0.003), and 1325.21 (P=0.0028), respectively. These data provide further insights into the biological basis of ALL highlighting the existence of both common and rare disease susceptibility variants. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305215 Fri, 02 Sep 2011 04:00:00 +0100 5305215 http://www.medworm.com/index.php?rid=5305217&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611004036%2Fabstract%3Frss%3Dyes We have read a recent article by Zhang et al. with great interest. The authors show that KIR2DS4 gene is associated with leukemia, particularly with CML, in Chinese Han patients. However, Zhang et al. do not differentiate between full length KIR2DS4 gene (KIR2DS4*001), encoding membrane-anchored cell surface receptor, and its variants (KIR2DS4*003,004,007) with 22-base pair deletion, which may encode only one-immunoglobulin-domain-possessing soluble molecule, not functioning as a cell surface receptor. One might argue that it appears not to matter much for Chinese Hans, as 72.7–79.0% of them possess KIR2DS4*001; nevertheless, 43.8–50.7% of this population (including some of those possessing KIR2DS4*001) are positive for KIR2DS4*003,004, and/or 007 deletant allele . Therefore, without h... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305217 Thu, 01 Sep 2011 04:00:00 +0100 5305217 http://www.medworm.com/index.php?rid=5170948&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003857%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5170948 Mon, 29 Aug 2011 15:56:30 +0100 5170948 http://www.medworm.com/index.php?rid=5305198&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003821%2Fabstract%3Frss%3Dyes Myelodysplastic syndromes (MDS) are heterogeneous disorders characterized by inefficient hematopoiesis, peripheral blood cytopenia and risk of progression to acute leukemia . The clinical heterogeneity of MDS is a reflection of the various pathogenic mechanisms responsible for their development. According to the prevailing dogma, clonal transformation would occur at the level of a committed myeloid stem cell that can give rise to red cells, platelets, and granulocytes. To manifest clinically, a myelodysplastic clone must pass several biologic milestones, i.e. enhanced self-renewal of a hematopoietic stem cell, acquisition of increased proliferative capacity, impaired differentiation, and genetic instability that may favour leukemic evolution. Each step in the process can be achieved by alt... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305198 Mon, 29 Aug 2011 04:00:00 +0100 5305198 http://www.medworm.com/index.php?rid=5305195&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003833%2Fabstract%3Frss%3Dyes The human T-lymphotropic retrovirus type 1 (HTLV-1) infects and immortalizes CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATL), an aggressive hematological malignancy that is resistant to most anticancer treatment modalities. With few exceptions, the clinical prognoses associated with advanced acute- and lymphoma-stage ATL are dismal – with typical patient life expectancies of 6months to 2years. There is an urgent need to develop improved chemotherapeutic strategies for the clinical management of HTLV-1-induced cancers. Herein, Zimmerman et al. report that the histone deacetylase inhibitors (HDAC-Is), valproic acid (VPA) and AR-42, induce histone hyperacetylation and apoptosis in HTLV-1-transformed T-cell-lines . As the in vivo efficacy of AR-42 has been previously demonstrate... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305195 Thu, 25 Aug 2011 04:00:00 +0100 5305195 http://www.medworm.com/index.php?rid=5388885&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100378X%2Fabstract%3Frss%3Dyes Anagrelide hydrochloride (AG) is an orally quinazoline derivative that reduces the platelet count through inhibition of the post-mitotic phases of megakaryocyte development. In Europe, AG was licensed in 2004 by the European Medicines Agency (EMEA) for the reduction of elevated platelet counts in high-risk essential thrombocythemia (ET) patients who are intolerant to, or whose elevated platelet counts are not reduced to an acceptable level by, their current therapy (usually hydroxycarbamide). Several studies have demonstrated its efficacy in lowering platelet count and reducing ET-associated symptoms [reviewed in ]. Owing to its inhibitory effect on cyclic AMP phosphodiesterase III, AG causes positive inotropic effects and vasodilation, leading to common side effects such as headache, tach... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388885 Fri, 19 Aug 2011 04:00:00 +0100 5388885 http://www.medworm.com/index.php?rid=5388884&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003791%2Fabstract%3Frss%3Dyes The therapeutic potential of allogeneic bone marrow transplantation (BMT) relies on the graft versus tumor (GVT) effect involving alloreactive donor T cells. Donor leukocyte infusions (DLI) following allogeneic BMT provide an unequivocal evidence for the potency GVT mediated by donor alloreactive T effector cells (Teffs) . However, alloreactive donor Teffs also cause graft versus host disease (GVHD), a major complication of allogeneic BMT. As such, GVHD and GVT activity are tightly linked and mechanisms that separate GVHD from GVT are not well understood. In this issue, Choi et al. explore the role of donor T cell subsets, the Teffs and donor regulatory T cells (Tregs), in the tumor microenvironment following delayed DLI. The data suggest while Tregs may suppress the bad, GVHD, they also h... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388884 Fri, 19 Aug 2011 04:00:00 +0100 5388884 http://www.medworm.com/index.php?rid=5305201&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003754%2Fabstract%3Frss%3Dyes Abstract: Considering current reliance on cancer registry data, we sought to assess the potential for bias in myelodysplastic syndrome (MDS) registration using SEER-Medicare data 2001–2005. Using a validated claims-based algorithm, we identified and compared registered and non-registered MDS patients, and found that median cumulative survival was 18 and 28 months, 74% and 64% used erythropoiesis-stimulating agents (ESAs), and average 6-month health care cost was $24,249 and $21,750, respectively. While most non-registered MDS patients showed resource utilization and survival characteristics consistent with lower-risk MDS, a subset was registered as acute myeloid leukemia (7.6%) and accounted for early mortality. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305201 Thu, 18 Aug 2011 04:00:00 +0100 5305201 http://www.medworm.com/index.php?rid=5388890&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003651%2Fabstract%3Frss%3Dyes Highlights: ► We assessed the relevance between HLA alleles and CML in Chinese population. ► A totality of 2281 CML cases and 41000 health controls was analyzed. ► HLA-A*11, A*74, HLA-B*40, B*47, B*55 and B*81 alleles increased the risk of CML. ► Nevertheless, HLA-DRB1*13 allele may contribute to the genetic protection to CML. ► Therefore certain HLA alleles may be associated with the pathogenesis of CML in Chinese.Abstract: Human leukocyte antigen (HLA) genetic polymorphisms are assumed to be correlated to the risk of chronic myelogenous leukemia (CML) in various ethnicities. Up to now, no clear consensus has been reached. Our goal is to address this issue in Chinese population. By searching the data in PubMed, Embase and four Chinese databases (prior to July 2010), the associat... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388890 Tue, 16 Aug 2011 04:00:00 +0100 5388890 http://www.medworm.com/index.php?rid=5305228&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003730%2Fabstract%3Frss%3Dyes We described for the first time hyperglycaemic metabolic off-target events during second-line treatment of imatinib resistant/intolerant patients with nilotinib : in order to document metabolic side effects, all of our CML patients treated with nilotinib, were assessed for total cholesterol, with HDL and LDL fraction, triglycerides, fasting glucose level and lipase at baseline, after 3, 6 and 12 months of treatment. Overall, 62 patients receiving nilotinib in our Institution were included in the analysis. Thirty patients all treated with 400mg BID, of whom 12 enrolled in phase II and IIIB sponsored Novartis trials, received the nilotinib as second-line treatment, and 32 received the drug as first-line treatment (27 patients enrolled in GIMEMA phase II trial and 5 patients enrolled in phase... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305228 Tue, 16 Aug 2011 04:00:00 +0100 5305228 http://www.medworm.com/index.php?rid=5305211&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003717%2Fabstract%3Frss%3Dyes Abstract: To understand the interactions between Notch1 and Ikaros in the evolution of T cell acute lymphoblastic leukemia (T-ALL), we traced the evolution of T-ALL in mice with an inherited Ikaros mutation, Ikzf1Plstc which inactivates DNA binding. DNA-binding Ikaros repressed Notch1 response in transfected cell lines and in CD4+8+ (DP) thymocytes from young pre-leukemic Ikzf1Plstc heterozygous mice. In DP thymocytes, a 50–1000 fold escalation in mRNA for Notch1 target genes Hes1 and Dtx1 preceded thymic lymphoma or leukemia and was closely correlated with the first detectable differentiation abnormalities, loss of heterozygosity (LOH) eliminating wild-type Ikzf1, and multiple missense and truncating Notch1 mutations. These findings illuminate the early stages of leukemogenesis by demon... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305211 Tue, 16 Aug 2011 04:00:00 +0100 5305211 http://www.medworm.com/index.php?rid=5305204&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003729%2Fabstract%3Frss%3Dyes Abstract: Brain damage related to intrathecal methotrexate in children with acute lymphoblastic leukemia (ALL) is still unclear. Neuroinflammatory mechanisms and intracerebral production of specific biomarkers, play a key role in determining neuroprotective mechanisms after brain injury. To determine whether the CSF concentrations of neuron-specific enolase (NSE), neurotrophic factors and doublecortin (DCX) are influenced by repeated intrathecal methotrexate administrations, we prospectively collected CSF samples from 10 children with ALL and 10 controls. Our results showed an increased expression of the liquoral markers. This up-regulation could be interpreted as a neuroprotective response of the brain against the neuronal damages induced by MTX. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305204 Tue, 16 Aug 2011 04:00:00 +0100 5305204 http://www.medworm.com/index.php?rid=5305194&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003675%2Fabstract%3Frss%3Dyes Abstract: Despite a startling separation of chronic lymphocytic leukemia (CLL) into two clinically different diseases with average survivals of 8 years and 25 years, the mutational status of immunoglobulin variable region (IGHV) genes has not entered routine clinical practice to assess prognosis, although its assessment is regarded as an essential for clinical trials. Instead, surrogates that may be measured by flow cytometry have been sought. Measurements of the expression of CD38 and ZAP-70 have been the most popular assays for prognosis although both are in their own ways unsatisfactory. Many other candidates have emerged, but none has been universally endorsed.As the assay for IGHV mutations has been standardized the level of difficulty has diminished and as greater numbers of cases ha... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305194 Tue, 16 Aug 2011 04:00:00 +0100 5305194 http://www.medworm.com/index.php?rid=5120524&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003456%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5120524 Fri, 12 Aug 2011 19:13:06 +0100 5120524 http://www.medworm.com/index.php?rid=5388886&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003663%2Fabstract%3Frss%3Dyes A number of different leukemias have shown associations with human leukocyte antigen (HLA) polymorphisms . One of the most commonly reported associations is between specific HLA alleles and chronic myelogenous leukemia (CML). Perhaps the most striking finding of these studies is that the specific associations with HLA alleles are rarely replicated. At first glance this is a puzzling observation, but it may offer some insight into the natural history of anti-cancer immune responses. Before we consider this question further, let's first step back and ask why HLA – leukemia associations may exist in the first place. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388886 Fri, 12 Aug 2011 04:00:00 +0100 5388886 http://www.medworm.com/index.php?rid=5495528&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003766%2Fabstract%3Frss%3Dyes Blastic plasmacytoid dendritic cell neoplasm (BPDCN), previously referred to as blastic NK-cell lymphoma or CD4+/CD56+ hematodermic neoplasm, is an extremely rare hematologic malignancy which is characterized by co-expression of CD4 and CD56 without any other lineage-specific markers . The disease was categorized as a type of NK-cell lymphoma, but is now classified as a rare subgroup of acute myeloid leukemia (AML) and related precursor myeloid neoplasms in the WHO classification 4th edition, because the precursor of plasmacytoid dendritic cells (pDCs) were identified as the origin of the malignancy . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495528 Wed, 10 Aug 2011 04:00:00 +0100 5495528 http://www.medworm.com/index.php?rid=5305226&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003687%2Fabstract%3Frss%3Dyes Scleromyxedema (SM) is a rare connective tissue disorder, also known as lichen myxedematosus. SM is usually characterized by symmetric eruption of small, firm, waxy non pruritic papules often arranged linearly usually on the face, neck, distal upper trunk, forearms, hands and thighs, sparing the palms, scalp and mucinous membranes. Diffuse mucin deposition within the glabella is observed in leonine facies . Patients present with scleroderma-like features with skin stiffness and decreased range of motion of the hands, lips, with limited mouth opening, and extremities that may result in significant disability. Systemic manifestations of SM may include Raynaud's phenomenon, esophageal dysmotility, laryngeal involvement, pulmonary involvement, including pulmonary hypertension, myopathy, renal ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305226 Wed, 10 Aug 2011 04:00:00 +0100 5305226 http://www.medworm.com/index.php?rid=5305224&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003390%2Fabstract%3Frss%3Dyes We described a patient who presents a chronic myelomonocytic leukemia (CMML) occurring very lately after the presence of a non sens mutation in the 3′ exon of the ATRX gene, and we reported CMML evolution on 5 azacytidine therapy. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305224 Wed, 10 Aug 2011 04:00:00 +0100 5305224 http://www.medworm.com/index.php?rid=5170953&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002700%2Fabstract%3Frss%3Dyes Abstract: Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing un... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5170953 Tue, 09 Aug 2011 23:00:00 +0100 5170953 http://www.medworm.com/index.php?rid=5305231&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003432%2Fabstract%3Frss%3Dyes Bendamustine is a mechlorethamine derivative with antimetabolic activity. Distinct from other alkylating agents, bendamustine includes a benzimidazole ring, whose structure mimics that of a purine analogue. It is approved for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) refractory to rituximab. It has also shown activity in multiple myeloma (MM). Several trials have examined the efficacy of bendamustine in advanced or treatment-resistant solid tumors, but clinical response has been limited. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305231 Mon, 08 Aug 2011 04:00:00 +0100 5305231 http://www.medworm.com/index.php?rid=5305223&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003699%2Fabstract%3Frss%3Dyes The chromosomal band 11q13 has been observed to be a common site of aberrations in many different hematological malignancies. However, only a few rearranged genes have been identified until recently such as CCND1 (cyclin D1) , NUMA1 (nuclear mitotic apparatus protein 1) and MACROD1 (MACRO domain-containing 1, which is also known as LRP16) . Therefore, we studied the 11q13 breakpoint in bone marrow cells of two patients with acute myeloid leukemia (AML). This region was analyzed using a fluorescent in situ hybridization (FISH) analysis, which was based on positional cloning strategy using a locus-specific probe for the cyclin D1 gene and a series of 6 bacterial artificial chromosome probes. In both patients, the 11q13 breakpoint was identified in an LRP5 gene (low-density lipoprotein recept... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305223 Mon, 08 Aug 2011 04:00:00 +0100 5305223 http://www.medworm.com/index.php?rid=5388902&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003596%2Fabstract%3Frss%3Dyes Highlights: ► We show that increased PLK1 expression in multiple myeloma is a poor prognostic factor. ► The PLK1 inhibitor BI 2536 is toxic to myeloma cell lines and murine myeloma xenografts. ► Further exploration of PLK1 as a therapeutic target in myeloma is warranted.Abstract: The amplified myeloma centrosome has been identified as a therapeutic target. The present study explored the expression and prognostic significance of the centrosome-associated protein PLK1 in myeloma and the effect of BI 2536, a potent and selective inhibitor of PLK1, on myeloma cells. High plasma cell expression of PLK1 protein in myeloma patient bone marrow biopsies is an independent adverse prognostic factor (HR=2.3, p=0.003 unadjusted; HR=1.9, p=0.03 in multivariable model). BI 2536 inhibits myeloma cel... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388902 Thu, 04 Aug 2011 04:00:00 +0100 5388902 http://www.medworm.com/index.php?rid=5495523&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003602%2Fabstract%3Frss%3Dyes In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n=115) and healthy controls (n=10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495523 Wed, 03 Aug 2011 04:00:00 +0100 5495523 http://www.medworm.com/index.php?rid=5170969&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003067%2Fabstract%3Frss%3Dyes This study shows that hematogones express surface ROR1 at an intermediate stage of maturation. ► Also, this study shows that less than 10% of B-ALL express surface ROR1. ► These ROR1+ B-ALL cases have an unusually high frequency of lacking CD34 and/or having t(1;19).Abstract: ROR1 is a receptor tyrosine kinase expressed during embryogenesis, on chronic lymphocytic leukemia (CLL) and in other malignancies. Hematogones (non-neoplastic B-lymphocyte precursors) express surface ROR1 at an intermediate stage of maturation that lacks CD34 or TdT. The neoplastic counterpart to hematogones is precursor-B acute lymphoblastic leukemia (B-ALL), but less than 10% of B-ALL express surface ROR1, and these ROR1+ B-ALL cases have an unusually high frequency of lacking CD34 and/or having t(1;19), a chro... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5170969 Tue, 02 Aug 2011 23:00:00 +0100 5170969 http://www.medworm.com/index.php?rid=5553081&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003407%2Fabstract%3Frss%3Dyes Abstract: Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) mutation have a poor prognosis, and FLT3 inhibitors are now under clinical investigation. PIM1, a serine/threonine kinase, is up-regulated in FLT3-ITD AML and may be involved in FLT3-mediated leukemogenesis. We employed a PIM1 inhibitor, AR00459339 (Array Biopharma Inc.), to investigate the effect of PIM1 inhibition in FLT3-mutant AML. Like FLT3 inhibitors, AR00459339 was preferentially cytotoxic to FLT3-ITD cells, as demonstrated in the MV4-11, Molm-14, and TF/ITD cell lines, as well as 12 FLT3-ITD primary samples. Unlike FLT3 inhibitors, AR00459339 did not suppress phosphorylation of FLT3, but did promote the de-phosphorylation of downstream FLT3 targets, STAT5, AKT, and BAD. Combining AR004... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553081 Mon, 01 Aug 2011 04:00:00 +0100 5553081 http://www.medworm.com/index.php?rid=5388900&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100333X%2Fabstract%3Frss%3Dyes Conclusion: Medical insurance and a systemic health education are extremely required for childhood ALL in low middle income countries. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388900 Mon, 01 Aug 2011 04:00:00 +0100 5388900 http://www.medworm.com/index.php?rid=5305227&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003419%2Fabstract%3Frss%3Dyes The ETV6 gene located at 12p13 encodes a transcription factor containing the 5′ helix-loop-helix dimerization domain and the 3′ ETS DNA-binding domain . Since the initial cloning from t(5;12)(q33;p13) in chronic myelomonocytic leukemia, ETV6 has been shown to be implicated in leukemia, lymphoma, myelodysplastic syndrome (MDS), and sarcoma through the formation of fusion genes by reciprocal translocations . More than 40 partner bands are associated with translocations involving ETV6, and at least 28 partner genes encoding protein tyrosine kinases, transcription factors, or other proteins, have been identified to date . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305227 Mon, 01 Aug 2011 04:00:00 +0100 5305227 http://www.medworm.com/index.php?rid=5305221&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003377%2Fabstract%3Frss%3Dyes We report here on a young adult with refractory cytopenia associated with an isolated i(5)(p10) that quickly evolved to acute myeloblastic leukemia (AML) showing a complex karyotype. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305221 Mon, 01 Aug 2011 04:00:00 +0100 5305221 http://www.medworm.com/index.php?rid=5305219&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003353%2Fabstract%3Frss%3Dyes We report here a patient with AML who presented with hypercalcemia and we evaluated several markers of bone turnover and osteoclast stimulators in an attempt to identify possible underlying mechanisms. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305219 Mon, 01 Aug 2011 04:00:00 +0100 5305219 http://www.medworm.com/index.php?rid=5305218&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003328%2Fabstract%3Frss%3Dyes Uterine localization of Non Hodgkin Lymphoma (NHL) represents a rare form of disease, occurring approximately in 0.5% of patients with NHL: uterus is a possible localization of a diffuse large B-cell NHL, while more primitive uterine NHL are rare . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305218 Mon, 01 Aug 2011 04:00:00 +0100 5305218 http://www.medworm.com/index.php?rid=5305214&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003365%2Fabstract%3Frss%3Dyes Abstract: We evaluated the prognostic value of serum ferritin (SF) level at diagnosis in 318 newly diagnosed IPSS low and int 1 (lower) risk MDS patients included in the French MDS registry, who did not require RBC transfusions and had baseline SF level determination. Increased baseline SF level (>300ng/ml) was correlated with male gender, more pronounced anaemia, and diagnosis of RARS but had no negative impact on progression to AML or survival. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305214 Mon, 01 Aug 2011 04:00:00 +0100 5305214 http://www.medworm.com/index.php?rid=5305208&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003584%2Fabstract%3Frss%3Dyes Abstract: Human T-lymphotropic virus type 1 (HTLV-1) causes a variety of forms of adult T-cell leukemia/lymphoma (ATL), a refractory CD4+/CD25+ T-cell malignancy. Novel approaches to treat ATL patients are required due to the resistance of ATL to conventional chemotherapies. Histone deacetylase inhibitors (HDACi), which induce histone hyperacetylation leading to chromatin remodeling and reactivation of transcriptionally repressed genes have shown efficacy against a variety of cancers. Herein, we tested if valproic acid and the novel orally bioavailable HDACi, AR-42 reduced the proliferation of ATL cell lines by promoting apoptosis and histone hyperacetylation. Both compounds were cytotoxic and elicited a dose dependent increase in cytochrome C and cleaved Poly (ADP-ribose) polymerase (PARP... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305208 Mon, 01 Aug 2011 04:00:00 +0100 5305208 http://www.medworm.com/index.php?rid=5120529&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002785%2Fabstract%3Frss%3Dyes In this issue of Leukemia Research, Yu and coworkers describe the interaction between mutated KIT and heat shock protein 90 (HSP90) in the Kasumi-1 cell line . This cell line harbors the AML-ETO hybride protein encoded by the t(8;21) fusion gene . This cytogenetic abnormality defines one of the core binding factor (CBF) variants of acute myeloid leukemia (AML) that is associated with a good prognosis , but even CBF-AML is heterogeneous and has a relapse risk of 30%. One of the most studied candidates causing heterogeneity within the CBF-AMLs is mutations in the receptor tyrosine kinase (RTK) KIT; these mutations are associated with a distinct gene expression signature in CBF-AML including deregulation of the nuclear factor-κB (NF-κB) pathway . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5120529 Sun, 31 Jul 2011 23:00:00 +0100 5120529 http://www.medworm.com/index.php?rid=5610115&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100302X%2Fabstract%3Frss%3Dyes Abstract: To study the role of SDF-1/CXCR4 axis in MDS, the expression of SDF-1 and CXCR4, VEGF, MVD and apoptosis were measured in MDS. The results showed that the expression of SDF-1 of the low-grade MDS is higher than that of the high-grade MDS and the control. The high-grade MDS had a significantly higher CXCR4 expression on CD34+ cell than low-grade MDS and the control. It was suggested that the SDF-1/CXCR4 axis play an important role in MDS. Apoptosis was significantly increased in low-grade MDS, compared with high-grade MDS. The expression of VEGF and MVD were higher in the high-grade MDS than in the low-grade MDS. There are positive correlations between SDF-1 and apoptosis in the low-grade MDS. For the high-grade MDS, there were positive correlations between CXCR4 and VEGF, and bet... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5610115 Fri, 29 Jul 2011 04:00:00 +0100 5610115 http://www.medworm.com/index.php?rid=5305222&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002529%2Fabstract%3Frss%3Dyes Monoclonal gammopathies are a heterogeneous group of disorders which include monoclonal gammopathy of unknown significance (MGUS), multiple myeloma (MM), solitary plasmacytoma, Waldenström's macroglobulinemia (WM), and primary amyloidosis. There is a known association between monoclonal gammopathy and neuropathy, however, the pathogenesis of this association has only recently been clarified. Several different neural antigenic sites have been identified, the most important of which is myelin-associated glycoprotein (MAG). Anti-MAG IgM is present in half of all patients with IgM monoclonal gammopathy-related neuropathy and it has therefore been suggested that reducing anti-MAG IgM may present a strategy to improve gammopathy-related neuropathy . (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305222 Fri, 29 Jul 2011 04:00:00 +0100 5305222 http://www.medworm.com/index.php?rid=5120568&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002803%2Fabstract%3Frss%3Dyes We describe such a patient where both CML and CLL responded to imatinib. To our knowledge this is the first description of a patient with CLL who has been treated with imatinib alone. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5120568 Thu, 28 Jul 2011 23:00:00 +0100 5120568 http://www.medworm.com/index.php?rid=5388905&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003341%2Fabstract%3Frss%3Dyes A 47-year-old male in chronic myeloid leukaemia (CML) blast crisis was transferred to our hospital for cord blood transplantation (CBT) in July 2008. His disease began in the chronic phase in July 2002, but his treatment was very unusual because he discontinued medicating himself many times. As an apparent result, an additional chromosomal abnormality of +8, +idem, and +der (12) appeared from March 2007, and the disease entered the accelerated phase. Although dasatinib was administered at 100mg/day from July 2008, there was no response and multiple subcutaneous nodules appeared as extramedullary CML invasions. There were no detectable ABL kinase mutations during the course of his disease. We began idarubicin (12mg/m2/day for 3 days) and cytarabine (100mg/m2/day for 1 week) chemotherapy, wh... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388905 Thu, 28 Jul 2011 04:00:00 +0100 5388905 http://www.medworm.com/index.php?rid=5388904&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003250%2Fabstract%3Frss%3Dyes Abstract: Although recent decades have seen a significant improvement in the treatment outcome of leukemia in the pediatric population, those who are treated for relapsed disease still face significant morbidity and mortality. However, current salvage regimens are often assembled with agents that have similar mode of activity as the chemotherapeutics used in the initial treatment. Hence, novel therapeutic agents that are capable of distinct and diverse mechanisms of activity in, now resistant, leukemia cells are of great interest. We have investigated the opioid agonist methadone for its anti-leukemic activity, initially reported in studies with cell lines derived from adult patients. Our findings show that, compared to normal cells, methadone has enhanced cytotoxicity against specimens an... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388904 Thu, 28 Jul 2011 04:00:00 +0100 5388904 http://www.medworm.com/index.php?rid=5388903&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003316%2Fabstract%3Frss%3Dyes Abstract: Synthetic glucocorticoids (GCs) form a crucial first-line treatment for childhood acute lymphoblastic leukemia (ALL). However prolonged GC therapy frequently leads to GC-resistance with an unclear molecular mechanism. 11β-hydroxysteroid dehydrogenase (11β-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11β-HSD2 expression in human T-cell leukemic cell lines. 11β-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11β-HSD inhibitor, carbenoxolone pre-treatment resulted in greater cell death with prednisolone assessed by methyl-thiazol-tetrazolium assay and caspase-3/7 assay, suggesting that 11β-HSD2 is a cause of GC-resistance in ALL. (Source: Leukemia Resear... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388903 Thu, 28 Jul 2011 04:00:00 +0100 5388903 http://www.medworm.com/index.php?rid=5305230&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003420%2Fabstract%3Frss%3Dyes In this study, we report a chronic myeloid leukemia (CML) case showing a TET2 single copy partial deletion associated to a t(4;6;11) rearrangement, appearing during the progression of the disease and responsible for a decreased TET2 gene expression. A putative role for TET2 haploinsufficiency in this patient's CML progression is discussed. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305230 Thu, 28 Jul 2011 04:00:00 +0100 5305230 http://www.medworm.com/index.php?rid=5305216&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003389%2Fabstract%3Frss%3Dyes LNK (SH2B3) is a member of a family of adaptor proteins that share a proline-rich N-terminal dimerization domain, a pleckstrin homology (PH) domain, a Src homology 2 (SH2) domain, and a conserved C-terminal tyrosine residue . It has been proposed as a putative tumor suppressor because it is a negative regulator of several cytokine receptors . LNK−/− mice exhibit a MPN-like phenotype with anomalies of hematopoiesis and abnormal accumulation of erythroid cells, megakaryocytes and B lymphocytes in different hematopoietic compartments . In addition, some genome-wide association studies have found that one SNP in exon 3 of this gene (rs3184504 and p.R262W) shows a significant association with eosinophil counts (a common feature of some MPNs), several blood parameters and hypertension . (Sou... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305216 Thu, 28 Jul 2011 04:00:00 +0100 5305216 http://www.medworm.com/index.php?rid=5305205&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002608%2Fabstract%3Frss%3Dyes Abstract: For more than 20 years erythropoietin (rHEPO) has largely been used to treat anemia in myelodysplastic syndromes (MDS). Early clinical trials showed erythroid responses in no more than 15–25% of patients. In the last decade, a better selection of MDS patients suitable for a therapeutic challenge with rHEPO, alone or in combination with G-CSF, allowed for an increased response-rate, averaging around 40%. More recently, an even higher percentage of responses have been obtained using higher-doses of rHEPO (up to 80,000IU/weekly) in lower-risk MDS patients. This treatment however, especially at such high doses, is costly and not easily affordable for prolonged periods. The aim of this study was to verify if the use of “standard” doses of rHEPO could induce a satisfying response... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305205 Thu, 28 Jul 2011 04:00:00 +0100 5305205 http://www.medworm.com/index.php?rid=5388887&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003262%2Fabstract%3Frss%3Dyes In this issue of Leukemia Research, Liu et al. present one of the largest case series to date on nine patients with a pathological diagnosis of HIV-negative plasmablastic lymphoma (PBL), and suggest that hematopoietic stem cell transplantation (HSCT) in first remission could derive on better outcomes in this rather aggressive B-cell lymphoma. PBL is a rare subtype of diffuse large B-cell lymphoma (DLBCL), which was initially described in patients with HIV infection. However, more recently, several cases of PBL have been identified in patients without HIV infection. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388887 Tue, 26 Jul 2011 04:00:00 +0100 5388887 http://www.medworm.com/index.php?rid=5553082&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003286%2Fabstract%3Frss%3Dyes Abstract: The function of the nucleolus is intimately connected to cell proliferation, division and growth. Many cancer cells have enlarged nucleoli, and several nucleolar proteins have been linked to tumorigenesis. In order to find proteins whose expression is altered in the nucleoli of leukemic cells, we carried out two-dimensional difference gel electrophoresis (2-D DIGE) analyses. Prohibitin (PHB) and TAR-DNA-binding protein-43 (TDP-43) were strongly expressed in the nucleoli of the pre-B-ALL cell line MHH-CALL3. Our results demonstrate that leukemic cells have differences in their nucleolar protein composition, and suggest that it may be possible to exploit these differences in identification of leukemia subtypes. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553082 Mon, 25 Jul 2011 04:00:00 +0100 5553082 http://www.medworm.com/index.php?rid=5388892&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003122%2Fabstract%3Frss%3Dyes Abstract: Among 9 children with myelodysplastic syndrome (MDS) and 18 children with juvenile myelomonocytic leukemia, one MDS patient with der(5;17)(p10;q10) exhibited deletion of the TP53 gene in one allele and mutation (410 T>A) in the other allele in myeloid and erythroid cells. Since the mutation was not detected in peripheral blood leukocytes 9 months before the diagnosis, biallelic somatic inactivation of the TP53 gene might play an important role in the occurrence of MDS. His poor outcome might be associated with resistance to chemotherapy/radiation of a minor clone with both TP53 gene alteration and MLL duplication that already existed at onset. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388892 Mon, 25 Jul 2011 04:00:00 +0100 5388892 http://www.medworm.com/index.php?rid=5388888&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003225%2Fabstract%3Frss%3Dyes Highlights: ► We investigated how the graft-versus-leukemia (GVL) activity induced by donor leukocyte infusion (DLI) after a haploidentical B6→F1 non-myeloablative allogeneic hematopoietic stem cell transplantation is attenuated at the tumor microenvironment. ► Aggravation of tumor growth was in line with a rebound in CD4+Foxp3+ regulatory T cells (Tregs) and a reduction in IFN-γ-producing effector T cells (Teffs). ► DLI-derived Tregs and Teffs may be potential indicators for maintenance of GVL activity after DLI in this GVL model.Abstract: We investigated how the graft-versus-leukemia (GVL) effect is attenuated in the tumor microenvironment using a murine model of non-myeloablative allo-HSCT (NM-HSCT) plus delayed donor leukocyte infusion (DLI) in a haploidentical B6→F1 strain ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388888 Mon, 25 Jul 2011 04:00:00 +0100 5388888 http://www.medworm.com/index.php?rid=5305210&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003298%2Fabstract%3Frss%3Dyes Highlights: ► Inhibition of NHE1 by cariporide in K562 decreases the pHi. ► VEGF secretion by K562 is inhibited upon cariporide treatment. ► HUVECs proliferation and migration are inhibited partially through decreased VEGF. ► In vitro tube formation is also inhibited partially by VEGF down-regulation. ► Microvessel density is decreased in cariporide treated K562 xenograft tumor.Abstract: To investigate the effect of inhibition of Na+/H+ exchanger isoform1 (NHE1) on K562 leukemia-driven angiogenesis, the selective NHE1 inhibitor cariporide was used. Cariporide treatment of K562 resulted in a decrease in pHi and down-regulation of VEGF secretion. The proliferation, migration and in vitro tube formation of human umbilical vein endothelial cells was decreased in cariporide treated K5... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305210 Mon, 25 Jul 2011 04:00:00 +0100 5305210 http://www.medworm.com/index.php?rid=5495521&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002207%2Fabstract%3Frss%3Dyes Abstract: Our retrospective analysis explored the role of leukemia cutis (LC) in disease progression of chronic myelomonocytic leukemia (CMML). Of 108 patients with CMML, 11 patients (10.2%) had LC including its equivalent (2 patients). Four of these patients developed acute myeloid leukemia (AML) within 0–4 months. The remaining 7 patients demonstrated increased monocytes ( (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495521 Fri, 22 Jul 2011 04:00:00 +0100 5495521 http://www.medworm.com/index.php?rid=5120531&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003110%2Fabstract%3Frss%3Dyes Advanced age has historically been considered an adverse indicator of prognosis in Chronic Myeloid Leukemia, as suggested by the Sokal and Hasford scoring systems . However, these prognostic scoring systems were created prior to the era of tyrosine kinase inhibitor therapy, when lesser tolerated agents such as interferon, or allogeneic transplantation were used more commonly. Therefore, the adverse prognosis in older patients may have reflected poor tolerance of these treatments, perhaps due to competing co-morbidities. Alternatively, the adverse prognosis in those with advanced age may have been a reflection of an intrinsic difference in disease biology, compared to younger CML patients. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5120531 Thu, 21 Jul 2011 23:00:00 +0100 5120531 http://www.medworm.com/index.php?rid=5305212&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003274%2Fabstract%3Frss%3Dyes Abstract: The use of WT1-specific CTL is one potential strategy to treat leukemic relapse following allogeneic stem cell transplant (SCT). Previous studies have largely focused on generating WT1-CTL from adult donors by cloning. We demonstrate that WT1-CTL can be generated from healthy adult donors and from cord blood by stimulating with an overlapping pool of peptides derived from full length WT1 and selecting antigen-specific cells based on the expression of CD137. The rapid expansion with anti-CD3 and IL-2 resulted in a 100–200-fold expansion. These CTL lysed WT1 expressing targets, including leukemia lines, in a HLA restricted manner. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305212 Thu, 21 Jul 2011 04:00:00 +0100 5305212 http://www.medworm.com/index.php?rid=5120533&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS014521261100275X%2Fabstract%3Frss%3Dyes Highlights: ► We assess the efficacy and safety of ATO combined with ATRA in the treatment of APL. ► ATO/ATRA improves the overall outcome of newly diagnosed and relapsed APL patients. ► ATO/ATRA is an effective treatment all APL patients previously untreated with ATO.Abstract: Arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) could induce apoptosis and differentiation in acute promyelocytic leukemia (APL) cells, respectively, thus the possibility of synergism between them was raised. This meta-analysis assessed the effectiveness and safety of ATO combined with ATRA in the treatment of APL. Compared with ATO alone, induction therapy with ATO/ATRA significantly increased the complete remission (CR) rate (RR: 1.08, 95% CI: 1.00–1.17, P=0.04), shortened the time to achieve CR ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5120533 Wed, 20 Jul 2011 23:00:00 +0100 5120533 http://www.medworm.com/index.php?rid=5388899&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003006%2Fabstract%3Frss%3Dyes Abstract: Diagnosis of MDS has changed during the last years because of the 2008 WHO classification. Complete blood cell count (CBC) is a very important tool both for diagnosis of MDS.The aim of this study was to evaluate if it is possible to use the abnormal signals produced by dysplastic cells to produce a flag “dysplasia” able to identify the patients needing further hematological investigations. The proposed flag has been tested in a large group of patients to evaluate the sensibility and specificity. We create 5 patterns of MDS. Our study demonstrated that the flag “dysplasia” is specific and sensible for MDS. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388899 Mon, 18 Jul 2011 04:00:00 +0100 5388899 http://www.medworm.com/index.php?rid=5388889&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003201%2Fabstract%3Frss%3Dyes In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388889 Mon, 18 Jul 2011 04:00:00 +0100 5388889 http://www.medworm.com/index.php?rid=5305229&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003237%2Fabstract%3Frss%3Dyes We report a B-cell ALL case with double Ph chromosome and three i(8)(q10) copies, as detected by conventional cytogenetics and fluorescent in situ hybridization (FISH). (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305229 Mon, 18 Jul 2011 04:00:00 +0100 5305229 http://www.medworm.com/index.php?rid=5305225&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003249%2Fabstract%3Frss%3Dyes Intracranial (IC) involvement is a rare complication of multiple myeloma (MM) reported in less than 1% of the patients; the prognosis is poor with median survivals of less than 1 month . At least two patterns of IC involvement have been described in MM: (i) osteodural (OD) localizations, characterized by the extension of bone lesions into the central nervous system (CNS) most frequently resulting from osseous lesions in the cranial vault and skull base or dural involvement and (ii) CNS localization characterized by intraparenchymal localizations, cerebral plasmacytomas or CNS myelomatosis, associated with dissemination of malignant plasma cells in the cerebrospinal fluid (CSF). Features predisposing to this complication are largely unknown. A recent review of the literature reported about ... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305225 Mon, 18 Jul 2011 04:00:00 +0100 5305225 http://www.medworm.com/index.php?rid=5305220&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003195%2Fabstract%3Frss%3Dyes Primary cutaneous CD30+ lymphoproliferative disorders are the second most common cutaneous T-cell lymphomas (CTCL), accounting for approximately 25% of all cases . It comprises a large spectrum of clinical and histological entities, with papulosis lymphomatoides and CD30+ anaplastic large cell lymphoma (ALCL) in opposite extremes. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305220 Mon, 18 Jul 2011 04:00:00 +0100 5305220 http://www.medworm.com/index.php?rid=5305206&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003043%2Fabstract%3Frss%3Dyes Abstract: Current strategies for detecting chromosome abnormalities in MDS/AML include FISH or traditional cytogenetics. MLPA detects abnormalities in multiple loci simultaneously, with higher resolution and throughput. Peripheral blood from 50 healthy subjects was used to establish probe-specific reference ranges, increasing MLPA sensitivity and specificity. MLPA was then performed on 110 FISH-tested blood or bone marrow samples from suspected leukemia patients. Our novel MLPA analysis system combined maximum stringency with sensitive detection of low-frequency abnormalities. Accuracy/specificity of MLPA were excellent compared to FISH. Our MLPA analysis/interpretation method provides a clinically robust, high-throughput, high-resolution option for detection of abnormalities associated wi... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305206 Mon, 18 Jul 2011 04:00:00 +0100 5305206 http://www.medworm.com/index.php?rid=5305197&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003213%2Fabstract%3Frss%3Dyes Lenalidomide is a milestone in the therapeutic management of myelodysplastic syndromes (MDS), especially in those with del 5q abnormalities. It is currently approved by the Food and Drug Administration for the treatment of low and intermediate-1 risk MDS patients with transfusion-dependent anemia associated with deletion 5q with or without additional chromosomal abnormalities. Lenalidomide belongs to a class of second generation immunomodulatory drugs (IMiDs) that traces its lineage to thalidomide. However, despite its success as a drug in MDS, the exact mechanism of action remains elusive. Several experimental studies have provided some hints. Wei et al. attributed the increased lenalidomide sensitivity of MDS patients with del 5q to the haploinsufficiency of two dual specificity phosphat... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305197 Mon, 18 Jul 2011 04:00:00 +0100 5305197 http://www.medworm.com/index.php?rid=5305196&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003183%2Fabstract%3Frss%3Dyes The rise of targeted agents for the treatment of cancer has resulted in the occasional replacement of cytotoxic chemotherapy with targeted immunotherapy, but more commonly with synergistic combinations of chemotherapy and immunotherapy resulting in improved response rates, disease free survivals, and even overall survivals compared to those possible with either alone. Synergy is usually defined as results from the combination of at least 2 agents which are better compared to what would be expected from adding the expected benefits of each agent. Synergy is often possible when the malignant target cells cannot be completely killed unless 2 different pathways are inhibited, so that either agent alone causes only partial activity. Another possible mechanism for synergy is when both agents are... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5305196 Mon, 18 Jul 2011 04:00:00 +0100 5305196 http://www.medworm.com/index.php?rid=5120551&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002815%2Fabstract%3Frss%3Dyes The efficacy of lenalidomide in the acquisition of transfusion independence and even cytogenetic remission in a high proportion of transfusion-dependent lower-risk patients with MDS and del(5q) has been demonstrated . However, it is not known whether the presence of a concomitant JAK2V617F mutation might influence such favorable results. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5120551 Sun, 17 Jul 2011 23:00:00 +0100 5120551 http://www.medworm.com/index.php?rid=5031335&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002839%2Fabstract%3Frss%3Dyes (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5031335 Sat, 16 Jul 2011 17:36:04 +0100 5031335 http://www.medworm.com/index.php?rid=5553074&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003109%2Fabstract%3Frss%3Dyes In conclusion our study demonstrated that a single dose of palonosetron plus a single dose of dexamethasone was effective in preventing CINV in patients treated with ABVD regimen. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5553074 Fri, 15 Jul 2011 04:00:00 +0100 5553074 http://www.medworm.com/index.php?rid=5495524&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003092%2Fabstract%3Frss%3Dyes Abstract: To evaluate the grading of fibrosis and immunohistochemical expression of MPL in bone marrow biopsies of ET and PMF. Fibrosis in bone marrow biopsies (BMBs) was evaluated according to the European Consensus for grading of fibrosis, according to reticulin proliferation. Immunohistochemical analysis was performed in samples from 18 ET and 38 PMF patients: 19 were classified as pre-fibrotic and 19 were classified as fibrotic according to the World Health Organization (WHO) criteria, by means of the MPL antibody. Six bone marrow donors’ biopsies were used as controls. Average reticulin (p (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5495524 Fri, 15 Jul 2011 04:00:00 +0100 5495524 http://www.medworm.com/index.php?rid=5388901&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611003018%2Fabstract%3Frss%3Dyes Abstract: We developed a simple, cost-effective, and accurate JAK2 allele burden quantification method named alternately binding probe competitive PCR (ABC-PCR). ABC-PCR can be performed to quantify target JAK2 allele burdens in a single reaction. The throughput and running cost of ABC-PCR are markedly improved compared with those of allele-specific quantitative PCR (AS-qPCR). The quantification of samples with known JAK2 allele burdens revealed that ABC-PCR had a small assay-to-assay variation. The JAK2 allele burdens in the patients with myeloproliferative neoplasms measured by ABC-PCR and AS-qPCR showed a good fitting. ABC-PCR would be a powerful tool for quantifying target JAK2 allele burdens. (Source: Leukemia Research) Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388901 Fri, 15 Jul 2011 04:00:00 +0100 5388901 http://www.medworm.com/index.php?rid=5388895&cid=s_36843_19_f&fid=36843&url=http%3A%2F%2Fwww.lrjournal.com%2Farticle%2FPIIS0145212611002979%2Fabstract%3Frss%3Dyes Abstract: Flow cytometric cell sorting combined with molecular gene rearrangement analysis was used to detect and to further characterize simultaneously occurring phenotypically distinct B cell monoclonal lymphoid and monoclonal plasma cell populations from 38 individual specimens. By sorting and subsequent gene rearrangement analysis, separate or identical monoclonality genotypes could be revealed and confirmed. In only 13 of 38 specimens, the B lymphoid cells and plasma cell populations showed an identical genotypic profile, while 25 had non-identical profiles (including 4 process control specimens). The majority of the genotypically identical group had a phenotype consistent with Waldenström's/lymphoplasmacytic lymphoma (WM/LPL), while WM/LPL phenotype was present in 16/25 of the non-i... Leukemia Research journals http://www.medworm.com/rss/comments.php?id=5388895 Fri, 15 Jul 2011 04:00:00 +0100 5388895