MedWorm: Chronic Leukemia

Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors [Microbiology]

Proceedings of the National Academy of Sciences — Tue, 16 Mar 2010 19:33:05 +0100

Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic... (Source: Proceedings of the National Academy of Sciences)

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A rare case of chronic myeloid leukemia with secondary chromosomal changes including partial trisomy 17q21 to 17qter and partial monosomy of 16p13.3

BioMed Central — Tue, 16 Mar 2010 00:00:00 +0100

Conclusion: Here a novel and cytogenetically unique case of a Ph chromosome positive CML clinically in chronic phase is reported, having complex secondary chromosomal aberrations. Thus, CML patients with complex chromosomal changes are nonetheless treatable by Imatinib. (Source: BioMed Central)

Safety profiles of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia

Journal of Clinical Nursing — Tue, 16 Mar 2010 00:00:00 +0100

Conclusions. There are known safety issues inherent to each TKI and close monitoring by nursing staff is necessary to identify and effectively manage AEs.Relevance to clinical practice. All three TKIs have demonstrated potential for fluid retention and cardiotoxicity. Nurses should be aware of how these AEs manifest and intervene appropriately. The safety profiles of these TKIs clearly differs and it is important to consider factors such as comorbidities when making treatment decisions. (Source: Journal of Clinical Nursing)

Cladribine and Fludarabine Equally Helpful for Progressive CLL

Medscape Hematology-Oncology Headlines — Mon, 15 Mar 2010 18:56:36 +0100

As first-line treatment for progressive chronic lymphocytic leukemia (CLL), cladribine and fludarabine are equally effective and safe in combination with cyclophosphamide, according to phase III trial results. Reuters Health Information (Source: Medscape Hematology-Oncology Headlines)

Health and risk behaviors in survivors of childhood acute myeloid leukemia: A report from the Children's Oncology Group

Pediatric Blood and Cancer — Mon, 15 Mar 2010 00:00:00 +0100

Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks.Participants were diagnosed with AML at (Source: Pediatric Blood and Cancer)

A role for PKR in hematologic malignancies

Journal of Cellular Physiology — Mon, 15 Mar 2010 00:00:00 +0100

The double-stranded RNA-dependent kinase PKR has been described for many years as strictly a pro-apoptotic kinase. Recent data suggest that the main purpose of this kinase is damage control and repair following stress and, if all else fails, apoptosis. Aberrant activation of PKR has been reported in numerous neurodegenerative diseases and cancer. Although a subset of myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia contain low levels of PKR expression and activity, elevated PKR activity and/or expression have been detected in a wide range of hematologic malignancies, from bone marrow failure disorders to acute leukemia. With the recent findings that cancers containing elevated PKR activity are highly sensitive to PKR inhibition, we explore the role of PKR in hematologic mal...

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BioSante Announces Positive Leukemia Vaccine Results

Health News from Medical News Today — Sun, 14 Mar 2010 07:00:00 +0100

BioSante Pharmaceuticals, Inc. (NASDAQ: BPAX) announced positive results of a human clinical study that show that its GVAX Leukemia vaccine may be able to reduce or eliminate the last remaining cancer cells in some chronic myeloid leukemia (CML) patients taking the drug Gleevec (imatinib mesylate). All patients enrolled in the trial used Gleevec for at least one year and still had cancer cells present. The study was conducted by researchers at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, led by Hyam Levitsky, M.D... (Source: Health News from Medical News Today)

BioSante Announces Positive Leukemia Vaccine Results

Immune System / Vaccines News From Medical News Today — Sun, 14 Mar 2010 07:00:00 +0100

Epidemiology and outcome of Rhodotorula infection in haematological patients

Mycoses — Fri, 12 Mar 2010 00:00:00 +0100

Rhodotorula spp. are emergent opportunistic pathogens, particularly in haematological patients. However, no systematic review of this infection has been undertaken in this high-risk patient group. The aim of this study was to review all reported cases of Rhodotorula infection to determine the epidemiology and outcome of this infection in this high-risk population. The 29 reported cases were fungaemias. The most common underlying haematological disorder was the presence of acute leukaemia (65.5%). Rhodotorula mucilaginosa was the species found more frequently (79.3%). Most cases (58.6%) had several risk factors ([ge]3) simultaneously. The most common predisposing factors were the presence of central venous catheter (CVC, 100%) and neutropenia (62.1%). A substantial number of patients (81.5%...

Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV

Blood — Thu, 11 Mar 2010 17:02:02 +0100

The role of allogeneic stem cell transplantation in chronic myeloid leukemia is being reevaluated. Whereas drug treatment has been shown to be superior in first-line treatment, data on allogeneic hematopoietic stem cell transplantation (allo SCT) as second-line therapy after imatinib failure are scarce. Using an interim safety analysis of the randomized German CML Study IV designed to optimize imatinib therapy by combination, dose escalation, and transplantation, we here report on 84 patients who underwent consecutive transplantation according to predefined criteria (low European Group for Blood and Marrow Transplantation [EBMT] score, imatinib failure, and advanced disease). Three-year survival after transplantation of 56 patients in chronic phase was 91% (median follow-up: 30 months). Tr...

Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia

Blood — Thu, 11 Mar 2010 17:02:02 +0100

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. When we investigated the presence of recurrent molecular lesions in a cohort of 49 children with JMML, neurofibromatosis phenotype (and thereby NF1 mutation) was present in 2 patients (4%), whereas previously described PTPN11, NRAS, and KRAS mutations were found in 53%, 4%, and 2% of cases, respectively. Consequently, a significant proportion of JMML patients without identifiable pathogenesis prompted our search for other molecular defects. When we applied single nucleotide polymorphism arrays to JMML patients, somatic uniparental disomy 11q was detected in 4 of 49 patients; all of these cases harbored RING finger domain c-Cbl mutations. In total, c...

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Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification

Blood — Thu, 11 Mar 2010 17:02:02 +0100

Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for which diagnostic criteria have been refined in the 2008 World Health Organization (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes (MDSs) and to AML with myelodysplasia-related changes (AML-MRC) is not clearly defined. We conducted a retrospective, multi-institutional study of patients with AEL and compared them with patients with MDS or AML-MRC with erythroid hyperplasia (≥ 50% erythroid cells). Among a total of 124 patients with AEL, 32% had a history of MDS or chronic cytopenia, 32% had therapy-related disease, and 35% had de novo disease. Sixty-four percent of patients had unfavorable AML risk-group karyotypes. FLT3 and RAS mutations were infrequent, occurring in 6% and...

Novel Therapeutic Agents Against Cancer Stem Cells of Chronic Myeloid Leukemia

Thu, 11 Mar 2010 13:49:34 +0100

(Source: Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents))

Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia

Leukemia — Thu, 11 Mar 2010 00:00:00 +0100

Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia Leukemia advance online publication, March 11, 2010. doi:10.1038/leu.2010.29 Authors: K Giannopoulos, A Dmoszynska, M Kowal, J Rolinski, E Gostick, D A Price, J Greiner, M Rojewski, S Stilgenbauer, H Döhner & M Schmitt (Source: Leukemia)

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells

Leukemia — Thu, 11 Mar 2010 00:00:00 +0100

Authors: T Vaisitti, S Aydin, D Rossi, F Cottino, L Bergui, G D'Arena, L Bonello, A L Horenstein, P Brennan, C Pepper, G Gaidano, F Malavasi & S Deaglio (Source: Leukemia)

Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence

Cancer — Thu, 11 Mar 2010 00:00:00 +0100

Monoclonal antibodies may be used more effectively in combination. A previous study of intravenous (iv) bolus alemtuzumab plus rituximab in patients with chronic lymphocytic leukemia (CLL) recurrence produced a response rate of 54% after a 4-week treatment period.To optimize dose, schedule, and route of alemtuzumab, a study was designed exploring continuous intravenous infusion (civ) followed by subcutaneous (sc) alemtuzumab together with weekly iv rituximab in patients with previously treated CLL.Data from 40 patients with a median age of 59 years, and a median of 3 prior regimens (range, 1-8 regimens) were evaluable. Approximately 64% of patients were fludarabine-refractory. Seven patients (18%) achieved a complete response (CR), 4 (10%) a nodular partial response (nPR), and 10 (25%) a p...

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Isoform-selective phosphoinositide 3-kinase inhibitors induce apoptosis in chronic lymphocytic leukaemia cells

British Journal of Haematology — Thu, 11 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Assessment of Peripheral Blood and Bone Marrow Cells Apoptosis Caused by Purine Analogues in Patients with Chronic Lymphocytic Leukemia in Correlation with Parameters of Disease Progression.

Acta Haematologica — Thu, 11 Mar 2010 00:00:00 +0100

Authors: Podhorecka M, Klimek P, Kowal M, Chocholska S, Bojarska-Junak A, Dmoszynska A Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with variable clinical course and prognosis. Therefore, the role of prognostic factors is very important, especially for identifying the group of patients who require intensive treatment. The aim of this study was to assess whether the rate of apoptosis caused by purine analogues differs between patients with better or worse prognostic factors. The experiments were preformed in cultures of blood and bone marrow obtained from CLL patients. The cultures were supplemented with cladribine and fludarabine. We determined the percentage of caspase-3-positive cells and the BCL-2/BAX ratio, and subsequently these apoptosis markers were correlated w...

Multidrug resistance gene (MDR1) polymorphisms correlate with imatinib response in chronic myeloid leukemia

Medical Oncology — Wed, 10 Mar 2010 16:02:53 +0100

In conclusion, determination of 1236T, C3435T, and G2677T MDR1 polymorphisms might be useful in response prediction to therapy with imatinib in patients with CML. Content Type Journal ArticleCategory Original paperDOI 10.1007/s12032-010-9456-9Authors Ling-Na Ni, Nanjing Medical University Department of Hematology, Jiangsu Province Hospital, The First Affiliated Nanjing Medical University Hospital 300 Guangzhou Rd 210029 Nanjing ChinaJian-Yong Li, Nanjing Medical University Department of Hematology, Jiangsu Province Hospital, The First Affiliated Nanjing Medical University Hospital 300 Guangzhou Rd 210029 Nanjing ChinaKou-Rong Miao, Nanjing Medical University Department of Hematology, Jiangsu Province Hospital, The First Affiliated Nanjing Medical University Hospital 300 Guangzhou R...

Identification of neoplastic cells in blood using the Sysmex XT-2000iV: a preliminary step in the diagnosis of canine leukemia

Veterinary Clinical Pathology — Wed, 10 Mar 2010 00:00:00 +0100

The objective of this study was to assess the capacity of the Sysmex XT-2000iV hematology analyzer to identify neoplastic cells in canine blood samples. Blood samples (n=160) were grouped into 5 categories: acute leukemia (n=30), chronic leukemia (n=15), neoplasia without blood involvement (n=41), non-neoplastic reactive conditions (n=31), and healthy dogs (n=43). WBC counts, WBC flags, scattergrams, percentages of cells with high fluorescence intensity, and percentages of cells in the lysis-resistant region were evaluated alone or in combination to establish a "leukemic flag." Sensitivity, specificity, negative (LR[minus]) and positive (LR+) likelihood ratios, and the number of false-negative (FN) and false-positive (FP) results were calculated, and receiver operating characteristic curve...

Detection of a gammaretrovirus, XMRV, in the human population: Open questions and implications for xenotransplantation

Retrovirology — Wed, 10 Mar 2010 00:00:00 +0100

XMRV (xenotropic murine leukaemia virus-related virus) is a gammaretrovirus that has been detected in human patients with prostate carcinoma, chronic fatigue syndrome (CFS) and also in a small percentage of clinically healthy individuals. It is not yet clear whether the distribution of this virus is primarily limited to the USA or whether it is causally associated with human disease. If future investigations confirm a broad distribution of XMRV and its association with disease, this would have an impact on xenotransplantation of porcine tissues and organs. Xenotransplantation is currently being developed to compensate for the increasing shortage of human material for the treatment of tissue and organ failure but could result in the transmission of porcine pathogens. Maintenance of pathogen...

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Phase III study shows cladribine and fludarabine equally effective for CLL when used in combination with cyclophosphamide

NeLM - News — Wed, 10 Mar 2010 00:00:00 +0100

Source: JCO Area: News According to research published early online in the Journal of Clinical Oncology, cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive chronic lymphocytic leukaemia (CLL). The PALG-CLL3 study involved a total of 423 patients and was conducted to compare the efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. Patients were randomised to receive cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (CC regimen, n=211) or fludarabine at 25 mg/m2 combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (FC regimen, n=212), every 28 days for up to six cycle...

Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia. A study of the Spanish PETHEMA group.

Haematologica — Wed, 10 Mar 2010 00:00:00 +0100

Conclusions These results indicate the benefit of early intervention during imatinib therapy. PMID: 20220063 [PubMed - as supplied by publisher] (Source: Haematologica)

The Oncogene DEK Promotes Leukemic Cell Survival and Is Downregulated by both Nutlin-3 and Chlorambucil in B-Chronic Lymphocytic Leukemic Cells.

Clinical Cancer Research — Tue, 09 Mar 2010 00:00:00 +0100

CONCLUSIONS: These data show that the downregulation of DEK in response to either Nutlin-3 or chlorambucil represents an important molecular determinant in the cytotoxic response of leukemic cells, and suggest that strategies aimed to downregulate DEK might improve the therapeutic potential of these drugs. Clin Cancer Res; 16(6); 1824-33. PMID: 20215548 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Sustained Molecular Response With Interferon Alfa Maintenance After Induction Therapy With Imatinib Plus Interferon Alfa in Patients With Chronic Myeloid Leukemia [Hematologic Malignancies]

Journal of Clinical Oncology — Mon, 08 Mar 2010 23:01:30 +0100

Conclusion Treatment with IFN enables discontinuation of imatinib in most patients after prior imatinib/IFN combination therapy and may result in improved molecular response. Induction of a proteinase-3–specific CTL response by IFN may contribute to this effect. (Source: Journal of Clinical Oncology)

Key Cause Of Chronic Leukemia Progression Identified By Study

Health News from Medical News Today — Mon, 08 Mar 2010 08:00:00 +0100

Researchers have discovered a key reason why a form of leukemia progresses from its more-treatable chronic phase to a life-threatening phase called blast crisis. The study, led by cancer researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), indicates that chronic myeloid leukemia (CML) progresses when immature white blood cells lose a molecule called miR-328. Loss of the molecule traps the cells in a rapidly growing, immature state... (Source: Health News from Medical News Today)

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Key Cause Of Chronic Leukemia Progression Identified By Study

Lymphoma / Leukemia News From Medical News Today — Mon, 08 Mar 2010 08:00:00 +0100

Second malignancies in B-cell chronic lymphocytic leukaemia: possible association with human papilloma virus

British Journal of Haematology — Mon, 08 Mar 2010 00:00:00 +0100

This report describes preliminary evidence for the presence of HPV in secondary malignancies, in patients with CLL. (Source: British Journal of Haematology)

Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells

Journal of Translational Medicine — Mon, 08 Mar 2010 00:00:00 +0100

Conclusions: We suggest to evaluate ZAP-70 expression in routine settings using the T/B Ratio-method, given the operator and laboratory independent feature of this approach. We propose the 3.0 T/B Ratio value as optimal cut-off to discriminate ZAP-70+ (T/B Ratio less than 3.0) from ZAP-70- (T/B Ratio more/equal than 3.0) cases. (Source: Journal of Translational Medicine)

Study identifies key cause of chronic leukemia progression

ScienceDaily Headlines — Fri, 05 Mar 2010 16:00:00 +0100

Researchers have discovered a key reason why chronic myeloid leukemia progresses from its more-treatable chronic phase to a life-threatening phase called blast crisis. The study indicates that CML progresses when immature white blood cells lose a molecule called miR-328 and this traps the cells in a rapidly growing, immature state. The research should provide a better understanding of the blast-crisis stage of CML, and it suggests a possible new treatment strategy for the disease. (Source: ScienceDaily Headlines)

Intracellular Succinylation of 8-Chloroadenosine and Its Effect on Fumarate Levels [Bioenergetics]

Journal of Biological Chemistry — Fri, 05 Mar 2010 14:37:12 +0100

8-Chloroadenosine (8-Cl-Ado) is a ribosyl nucleoside analog currently in phase I testing for the treatment of chronic lymphocytic leukemia (CLL). 8-Cl-Ado activity is dependent on adenosine kinase and requires intracellular accumulation of 8-Cl-Ado as mono-, di-, and tri-phosphates. In the current study with four mantle cell lymphoma cell lines, we report a new major metabolic pathway for 8-Cl-Ado intracellular metabolism, the formation of succinyl-8-chloro-adenosine (S-8-Cl-Ado) and its monophosphate (S-8-Cl-AMP). 8-Cl-AMP levels were highly associated with S-8-Cl-AMP levels and reached a steady-state prior to the secondary metabolites, 8-Cl-ATP and S-8-Cl-Ado. Consistent with fumarate as a required substrate for formation of succinyl-8-Cl-adenylate metabolites, the S-8-Cl-adenylate conce...

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Successful Peripheral Blood Stem Cells Collection in Imatinib Pretreated and Nilotinib-Treated Chronic Myeloid Leukemia Patient

Journal of Oncology — Fri, 05 Mar 2010 13:48:30 +0100

We report a case of a successful mobilization and harvest of the peripheral blood stem cells (PBSCs) in imatinib-pretreated and nilotinib treated 52-year-old woman diagnosed with Philadelphia chromosome-positive and BCR-ABL (b2a2) positive chronic phase CML in 2/2002. She failed interferon-alfa and imatinib treatment. She achieved her first complete molecular remission after 16 months of nilotinib treatment and later on was mobilized with filgrastim at a dose of 10 ug/kg/day applied subcutaneously once daily. The total number of 2.98×106 CD34+ cells/kg was harvested on the fourth day of the mobilization. The autologous graft of the stem cells was cryopreserved and tested for the residual disease: the FISH revealed negative results and the RT-PCR was positive (BCR-ABL/A...

Molecular diagnostics in chronic myeloid leukemia

Expert Opinion: Expert Opinion on Medical Diagnostics — Fri, 05 Mar 2010 10:51:47 +0100

Expert Opinion on Medical Diagnostics , March 2010, Vol. 4, No. 2, Pages 113-124. (Source: Expert Opinion: Expert Opinion on Medical Diagnostics)

NICE Set To Recommend Rituximab For Relapsed Or Refractory Chronic Lymphocytic Leukaemia

Health News from Medical News Today — Fri, 05 Mar 2010 04:00:00 +0100

The National Institute for Health and Clinical Excellence (NICE) has today (4 March) issued final draft guidance recommending the drug rituximab(MabThera) as a treatment for certain patients with relapsed or refractory chronic lymphocytic leukaemia. This draft is now with consultees who have the opportunity to appeal against the proposed recommendations before final guidance is published later this year. Chronic lymphocytic leukaemia is a cancer of the white blood cells and is the most common form of leukaemia in the UK... (Source: Health News from Medical News Today)

NICE Set To Recommend Rituximab For Relapsed Or Refractory Chronic Lymphocytic Leukaemia

Cancer / Oncology News From Medical News Today — Fri, 05 Mar 2010 04:00:00 +0100

Key cause of chronic leukemia progression

Medicineworld.org: New Article Alert — Fri, 05 Mar 2010 03:04:28 +0100

COLUMBUS, Ohio Scientists have discovered a key reason why a form of leukemia progresses from its more-treatable chronic phase to a life-threatening phase called blast crisis. The study, led by cancer scientists at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), indicates that chronic myeloid leukemia (CML) progresses when immature white blood cells lose a molecule called miR-328........ (Source: Medicineworld.org: New Article Alert)

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Pelvic radiotherapy and the risk of secondary leukemia and multiple myeloma

Cancer — Fri, 05 Mar 2010 00:00:00 +0100

Although several studies had examined secondary malignancies in patients with specific primary tumor types, to the authors' knowledge there are very few data examining the long-term sequelae of pelvic radiation as a whole. The goal of the current study was to examine the risk of treatment-associated leukemia and multiple myeloma in patients treated with pelvic radiotherapy.Patients with invasive tumors of the vulva, cervix, uterus, anus, and rectosigmoid treated from 1973 to 2005 and recorded in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified based on receipt of pelvic radiotherapy. The incidence of secondary leukemia (except chronic lymphocytic leukemia) and multiple myeloma were examined. Multivariate Cox proportional hazards models...

Overexpression of Apg-2 increases cell proliferation and protects from oxidative damage in BaF3-BCR/ABL cells.

International Journal of Oncology — Thu, 04 Mar 2010 22:59:00 +0100

Authors: Li C, Liu D, Yuan Y, Huang S, Shi M, Tao K, Feng W Apg-2, a mammalian heat-shock protein belonging to the heat-shock protein 110 (Hsp110) family, was previously found to be overexpressed in BaF3-BCR/ABL cells that were treated with hydrogen peroxide (H2O2) through our comparative proteomics study. The expression of Apg-2 in chronic myelogenous leukemia (CML) cells and its role have not been investigated, forming the basis for this study. BaF3-MIGR1 and BaF3-BCR/ABL cell lines stably overexpressing Apg-2 were established and exposed to 50 microM H2O2 for 10 min. Western blot analysis of Apg-2 expression confirmed that H2O2 treatment significantly up-regulated Apg-2 expression. Apg-2 overexpression elevated BaF3-BCR/ABL cell proportions in S and G2/M phase, increased cell prolif...

Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression

Blood — Thu, 04 Mar 2010 17:00:46 +0100

This study demonstrates the existence of separate MV phenotypes during leukemic disease progression and underscores the important role of MVs in activation of the tumor microenvironment. (Source: Blood)

Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia

Blood — Thu, 04 Mar 2010 17:00:45 +0100

The aim of this study was to determine the efficacy and safety of treatment of pediatric acute promyelocytic leukemia (APL) with single-agent arsenic trioxide (ATO). A total of 19 children (≤ 15 years of age) with newly diagnosed APL were treated with single-agent ATO for remission induction and postremission therapy. Seventeen of the children (89.5%) achieved complete hematologic remission, and 2 early deaths occurred from intracranial hemorrhage. ATO-induced leukocytosis was observed in 13 (68.4%) patients. Other ATO-related toxicities were minimal and transient. Postremission ATO therapy continued for 3 years; the most common side effect was ATO-induced neutropenia. With a median follow-up of 53 months (range, 23-76 months), the calculated 5-year overall survival and event-free survi...

Pharmacological activation of the p53 pathway in haematological malignancies

Journal of Clinical Pathology — Thu, 04 Mar 2010 15:42:49 +0100

p53 gene mutations are rarely detected at diagnosis in common haematological cancers such as multiple myeloma (MM), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL) and Hodgkin's disease (HD), although their prevalence may increase with progression to more aggressive or advanced stages. Therapeutic induction of p53 might therefore be particularly suitable for the treatment of haematological malignancies. Some of the anti-tumour activity of current chemotherapeutics has been derived from activation of p53. However, until recently it was unknown whether p53 signalling is functional in certain haematological cancers including MM and if p53 activity is sufficient to trigger an apoptotic response. With the recent discovery of nutlins, which represent the first highly selective...

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Study identifies key cause of chronic leukemia progression

EurekAlert! - Medicine and Health — Thu, 04 Mar 2010 05:00:00 +0100

(Ohio State University Medical Center) Researchers have discovered a key reason why chronic myeloid leukemia progresses from its more-treatable chronic phase to a life-threatening phase called blast crisis. The study indicates that CML progresses when immature white blood cells lose a molecule called miR-328 and this traps the cells in a rapidly growing, immature state. The research should provide a better understanding of the blast-crisis stage of CML, and it suggests a possible new treatment strategy for the disease. (Source: EurekAlert! - Medicine and Health)

Role of BCR-ABL-Y177-mediated p27kip1 phosphorylation and cytoplasmic localization in enhanced proliferation of chronic myeloid leukemia progenitors

Leukemia — Thu, 04 Mar 2010 00:00:00 +0100

Authors: S Chu, T McDonald & R Bhatia (Source: Leukemia)

NICE issues Final Appraisal Determination on rituximab for relapsed chronic lymphocytic leukaemia

NeLM - News — Thu, 04 Mar 2010 00:00:00 +0100

Source: NICE Area: News NICE has issued its Final Appraisal Determination on rituximab for relapsed chronic lymphocytic leukaemia, which contained the following preliminary recommendations: . Rituximab in combination with fludarabine and cyclophosphamide is recommended as a treatment option for people with relapsed or refractory chronic lymphocytic leukaemia except when the condition is refractory to fludarabine (i.e. not responded to fludarabine or has relapsed within 6 months of treatment) or has previously been treated with rituximab. . Rituximab in combination with fludarabine and cyclophosphamide is recommended only in the context of research for people with relapsed or refractory chronic lymphocytic leukaemia that has previously been treated with ritu...

NICE issues Final Appraisal Determination on azacitidine

NeLM - News — Thu, 04 Mar 2010 00:00:00 +0100

Source: NICE Area: News NICE has prepared a Final Appraisal Determination on azacitidine for the treatment of myelodyplastic syndrome, chronic myelomonocytic leukaemia, and acute myeloid leukaemia, which stated that azacitidine is not recommended as a treatment option for people who have the following conditions and are not eligible for haematopoietic stem cell transplantation: . Intermediate-2 and high-risk myelodysplastic syndromes according to the International Prognostic Scoring System. . Chronic myelomonocytic leukaemia with 10-29% marrow blasts without myeloproliferative disorder. . Acute myeloid leukaemia with 20-30% blasts and multilineage dysplasia, according to the WHO classification. The appeal period for this appraisal...

ARIAD Receives Orphan Drug Designations For Its Investigational Pan BCR-ABL Inhibitor, AP24534, In Chronic Myeloid Leukemia

Cancer / Oncology News From Medical News Today — Wed, 03 Mar 2010 10:00:00 +0100

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ARIAD Receives Orphan Drug Designations For Its Investigational Pan BCR-ABL Inhibitor, AP24534, In Chronic Myeloid Leukemia

Health News from Medical News Today — Wed, 03 Mar 2010 10:00:00 +0100

ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) announced that its investigational pan-BCR-ABL inhibitor, AP24534, has been granted orphan drug designation by both the U. S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). In the U.S., the orphan designation of AP24534 is for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and in the E.U., its orphan designation is for CML and acute lymphoblastic leukemia... (Source: Health News from Medical News Today)

U.S. Food And Drug Administration (FDA) Sets 22 March For Oncologic Drugs Advisory Committee (ODAC) Meeting To Review OMAPRO™

Health News from Medical News Today — Wed, 03 Mar 2010 09:00:00 +0100

ChemGenex Pharmaceuticals Limited (ASX:CXS) announced that the U.S. Food and Drug Administration (FDA) has rescheduled the previously postponed Oncologic Drugs Advisory Committee (ODAC) meeting to 22 March 2010. The ODAC meeting will consider ChemGenex's application for OMAPRO™ (omacetaxine mepesuccinate) for the treatment of adults with chronic myeloid leukemia (CML) who have failed prior therapy with imatinib and who have developed the Bcr-Abl T315I mutation... (Source: Health News from Medical News Today)

Molecular Monitoring of BCR-ABL Transcripts in Patients With Chronic Myelogenous Leukemia: Is High Sensitivity of Clinical Value?

Current Hematologic Malignancy Reports — Wed, 03 Mar 2010 08:07:57 +0100

Abstract Monitoring of disease response during treatment with tyrosine kinase inhibitors of patients with chronic myelogenous leukemia dramatically changed after the introduction of real-time PCR, which allows quantification of BCR-ABL transcript levels with high sensitivity and precision. However, its role in patients who have achieved complete cytogenetic response is not entirely clear; incorrect interpretation of results could lead to unnecessary changes from an effective treatment. This review discusses the current evidence regarding the benefits, uncertainties, and potential drawbacks of molecular monitoring in patients with chronic myelogenous leukemia in chronic phase. Content Type Journal ArticleDOI 10.1007/s11899-010-0046-xAuthors Maxim Norkin, Wayne State U...

Summary of 615 patients of chronic myeloid leukemia in Shanghai from 2001 to 2006

Journal of Experimental and Clinical Cancer Research — Wed, 03 Mar 2010 00:00:00 +0100

Conclusions: The number of new patients arising in Shanghai increased from 2001 to 2006. There were still patients receiving hydroxyurea and IFN-alpha. As the first-line regime for CML, imatinib was less administered in Shanghai before, but has received considerable development and great responses since 2003. (Source: Journal of Experimental and Clinical Cancer Research)

Transcribed-ultra conserved region expression profiling from low-input total RNA

BMC Genomics - Latest articles — Wed, 03 Mar 2010 00:00:00 +0100

Conclusions: We demonstrated that the quantification procedure shown here is an accurate and reliable technique for genome-wide non coding gene (i.e., UCRs) profiling using small amounts of RNA. This issue is particularly important because studies of transcription regulation are increasingly conducted in small homogeneous samples, such as laser capture microdissected or sorted cell populations. (Source: BMC Genomics - Latest articles)

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Chronic Myelogenous Leukemia

Clinical Care Options Oncology - Leukemia — Tue, 02 Mar 2010 12:00:00 +0100

Learning Module - Join Brian Druker, MD; Elias Jabbour, MD; Neil P. Shah, MD, PhD; and Moshe Talpaz, MD, as they review the clinical implications of research on chronic myelogenous leukemia presented at the 2009 Hematology meeting. (Source: Clinical Care Options Oncology - Leukemia)

Tyrosine Kinase Inhibitors: The First Decade

Current Hematologic Malignancy Reports — Tue, 02 Mar 2010 10:07:57 +0100

Abstract The treatment of chronic myeloid leukemia (CML) drastically changed with the introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), in 1998. By directly targeting this leukemogenic protein kinase, imatinib affords patients with CML sustained chromosomal remissions, which translate into prolonged survival. However, there has been concern over the emergence of resistance to imatinib, and some patients fail to respond or are intolerant of imatinib therapy because of untoward toxicity. This has spurred interest in developing novel TKIs to overcome the mechanisms of resistance that lead to treatment failure—most importantly, Bcr-Abl1 kinase domain mutations. Two of these second-generation TKIs, nilotinib and dasatinib, are approved worldwide f...

Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies

Annals of Hematology — Tue, 02 Mar 2010 10:00:21 +0100

Abstract Despite recent progress in molecular research in myeloid malignancies, in subsets of patients with myelodysplastic syndrome (MDS) so far no underlying mutation was identified. In the myeloproliferative neoplasms (MPNs), the JAK2V617F alone cannot explain the phenotypic heterogeneity. In acute myeloid leukemia (AML), clinical variability exists within distinct subgroups. Thus, the search for novel molecular markers continues. Recently, mutations of the tet oncogene family member 2 (TET2) and Casitas B-cell lymphoma (CBL) genes became the focus of interest. With diverse genetic methods, TET2 on chromosome 4q24 was identified as candidate tumor suppressor gene. Sequencing studies revealed heterogeneous mutations in 10–25% of patients with acute myeloid leukemia (AML)...

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

Cytometry Part B: Clinical Cytometry — Tue, 02 Mar 2010 00:00:00 +0100

p53 is a cell cycle checkpoint control protein that assesses DNA damage and acts as a transcription factor regulating genes, which control cell growth, DNA repair, and apoptosis. p53 mutations have been found in a wide variety of different cancers including flow cytometric assessment of p53 protein expression using anti-p53 monoclonal antibodies. We studied p53 protein expression by flow cytometry (FC) assay in 223 blood and/or bone marrow samples from 72 patients with chronic myeloid leukemia (CML): 54 in chronic phase (CML-CP), 7 in accelerated phase (CML-AP), and 11 in blastic phase (CML-BP); 64 patients with chronic lymphoid leukemia (CLL): (34 at diagnosis, 21 in previously treated, and 9 with Richter's syndrome); 44 patients with acute lymphoid leukemia (ALL): 36 at diagnosis and 8 i...

Chronic Treatment with an Oral Rho-Kinase Inhibitor Restores Erectile Function by Suppressing Corporal Apoptosis in Diabetic Rats

The Journal of Sexual Medicine — Tue, 02 Mar 2010 00:00:00 +0100

Conclusions. This study indicates that up-regulation of the penile RhoA/ROCK pathway in diabetic rats enhances corporal apoptosis via the PTEN/Akt pathway resulting in ED, which could be prevented by chronic treatment with fasudil. Li WJ, Park K, Paick J-S, and Kim SW. Chronic treatment with an oral rho-kinase inhibitor restores erectile function by suppressing corporal apoptosis in diabetic rats. J Sex Med **;**:**[ndash]**. (Source: The Journal of Sexual Medicine)

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Narrative Review: Thrombocytosis, Polycythemia Vera, and JAK2 Mutations: The Phenotypic Mimicry of Chronic Myeloproliferation.

Annals of Internal Medicine — Tue, 02 Mar 2010 00:00:00 +0100

Authors: Spivak JL The myeloproliferative disorders polycythemia vera, essential thrombocytosis, and primary myelofibrosis are clonal disorders arising in a pluripotent hematopoietic stem cell, causing an unregulated increase in the number of erythrocytes, leukocytes, or platelets, alone or in combination; eventual marrow dominance by the progeny of the involved stem cell; and a tendency to arterial or venous thrombosis, marrow fibrosis, splenomegaly, or transformation to acute leukemia, albeit at widely varying frequencies. The discovery of an activating mutation (V617F) in the gene for JAK2 (Janus kinase 2), a tyrosine kinase utilized by hematopoietic cell receptors for erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor, provided an explanation for the shared c...

New Developments in Tyrosine Kinase Inhibitor Therapy for Newly Diagnosed Chronic Myeloid Leukemia.

Clinical Cancer Research — Tue, 02 Mar 2010 00:00:00 +0100

Authors: le Coutre P, Schwarz M, Kim TD The biology of chronic myeloid leukemia (CML) has enabled pioneering studies with targeted therapies. BCR-ABL inhibition with imatinib results in high levels of efficacy in patients with newly diagnosed CML in chronic phase (CP), but an estimated 35% of patients could benefit from more effective treatment. Several novel treatment strategies are being investigated in newly diagnosed CML-CP. These strategies include upfront treatment with next-generation tyrosine kinase inhibitors, such as dasatinib, nilotinib, or bosutinib, which also target BCR-ABL but with increased in vitro potency compared with imatinib, and possibly a reduced potential for resistance. Recent in vitro studies have shown that short-term exposure to dasatinib or continuous expos...

Sequential treatment with flavopiridol synergistically enhances pyrrolo-1,5-benzoxazepine-induced apoptosis in human chronic myeloid leukaemia cells including those resistant to imatinib treatment.

Biochemical Pharmacology — Tue, 02 Mar 2010 00:00:00 +0100

In conclusion, results from this study highlight the potential of these novel series of PBOX compounds, alone or in sequential combination with flavopiridol, as an effective therapy against CML. PMID: 20206141 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)

Kinase inhibitors: A winning combination against BCR–ABL

Nature Reviews Drug Discovery — Mon, 01 Mar 2010 14:48:42 +0100

Kinase inhibitors: A winning combination against BCR–ABL Nature Reviews Drug Discovery 9, 194 (2010). doi:10.1038/nrd3119 Author: Monica Hoyos Flight In chronic myelogenous leukaemia (CML), a reciprocal translocation between chromosomes 9 and 22 results in a gene encoding BCR–ABL, a fused deregulated kinase that stimulates cellular proliferation and mediates resistance to apoptosis. Although inhibitors directed against the ATP-binding site of the kinase, such as imatinib (Source: Nature Reviews Drug Discovery)

The Lysosomotropic Agent, Hydroxychloroquine, Delivered in a Biodegradable Nanoparticle System, Overcomes Drug Resistance of B-Chronic Lymphocytic Leukemia Cells In Vitro

Cancer Biotherapy and Radiopharmaceuticals — Mon, 01 Mar 2010 04:56:46 +0100

Cancer Biotherapy & Radiopharmaceuticals Feb 2010, Vol. 25, No. 1: 97-103. (Source: Cancer Biotherapy and Radiopharmaceuticals)

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Avoidance, Sobriety and Reality: The Psychology of Addiction

Psychology Today Addiction Center — Mon, 01 Mar 2010 03:51:22 +0100

Despite their limitations, preconceptions, and borderline exploitation, the various recent television reality shows about addiction do shine a bright and dramatic light on two dark, secretive, debilitating and very destructive mental disorders: Substance Abuse and Substance Dependence. Like many, but especially as a clinical and forensic psychologist with almost thirty-five years of dealing with such tragic tales, I still find it simultaneously fascinating and painful to watch shows like Intervention and Celebrity Rehab with "Dr. Drew" Pinsky. I suspect I am not unlike other ambivalent viewers who stop channel-surfing long enough to gawk at the emotional equivalent of a human car wreck. Despite being disturbed, horrified and racked with voyeuristic guilt, we just can't quit watching. Still...

Unexpected detection of monoclonal B-cell lymphocytosis in a HLA-matched sibling donor on the day of allogeneic stem cell transplantation for a patient with chronic lymphocytic leukaemia: clinical outcome

British Journal of Haematology — Mon, 01 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Dynamic contrast enhanced magnetic resonance imaging of diffuse spinal bone marrow infiltration in patients with hematological malignancies.

Korean J Radiol — Mon, 01 Mar 2010 00:00:00 +0100

CONCLUSION: DCE-MRI of spine can be a useful tool in detecting diffuse marrow infiltration of hematological malignancies, while its parameters including E(max), ES, and TTP can reflect the malignancies' histological grade. PMID: 20191066 [PubMed - in process] (Source: Korean J Radiol)

Urolithiasis in patients suffering from malignant hematologic diseases.

Yonsei Medical Journal — Mon, 01 Mar 2010 00:00:00 +0100

CONCLUSION: The incidence of urolithiasis for malignant hematologic patients was significantly higher than that for the control group. PMID: 20191017 [PubMed - in process] (Source: Yonsei Medical Journal)

Results of hematopoietic stem cell transplant in shiraz: 15 years experience in southern iran.

Mon, 01 Mar 2010 00:00:00 +0100

Conclusions: These data reflect the important role of hematopoietic stem cell transplant in improving survival for a variety of hematopoietic system disorders at our center in Southern Iran. In patients with B-thalassemia major hematopoietic stem cell transplant seems to be the treatment of choice, because it leads to a cure in all classes (Lucarelli risk group, I-III). Based on high success rates in patients with class II and III thalassemia with the addition of the antithymocyte globulin to conditioning regimen of stem cell transplant, we also recommend using this new method of conditioning in transplant of thalassemia patients. PMID: 20199373 [PubMed - in process] (Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantati...

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Montana Court Rules in Favor of Aid in Dying

Internal Medicine News — Mon, 01 Mar 2010 00:00:00 +0100

Physicians in Montana may legally assist terminally ill patients in hastening death, according to a ruling by the Montana Supreme Court. The decision in the case of Baxter v. State of Montana concerned Robert Baxter, a retired truck driver from Billings, Mont., who was terminally ill with lymphocytic leukemia with diffuse lymphadenopathy. As a result of the disease and its treatment, Mr. Baxter suffered from symptoms including “infections, chronic fatigue and weakness, anemia, night sweats, nausea, massively swollen glands, significant ongoing digestive problems, and generalized pain and discomfort,” according to the decision. (Source: Internal Medicine News)

Genetic modification of primary chronic lymphocytic leukemia cells with a lentivirus expressing CD38.

Haematologica — Mon, 01 Mar 2010 00:00:00 +0100

Authors: Pearce L, Morgan L, Lin TT, Hewamana S, Matthews RJ, Deaglio S, Rowntree C, Fegan C, Pepper C, Brennan P Studies of the role of individual genes in chronic lymphocytic leukemia (CLL) have been hampered by the inability to consistently transfect primary tumor cells. Here, we describe a highly efficient method of genetically modifying primary CLL cells using a VSVG pseudotyped lentiviral vector. We transduced CD38 negative CLL cells with a lentiviral vector encoding CD38 which caused increased surface CD38 expression in all the samples tested (n=17) with no evidence of plasmacytoid differentiation. The mean percentage of positive cells expressing CD38 was 87%+/-8.5% and the mean cell viability 74%+/-17%. This high level of transduction of all the CLL cell samples tested demonstr...

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

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Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

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Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

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Three paths to better tyrosine kinase inhibition behind the blood-brain barrier in treating chronic myelogenous leukemia and glioblastoma with imatinib.

Clinical Trials And Noteworthy Treatments For Brain Tumors — Sun, 28 Feb 2010 16:12:00 +0100

(Source: Clinical Trials And Noteworthy Treatments For Brain Tumors)

Safe switching from dasatinib to nilotinib after a 1-month off-drug period for persistent pleural effusion in patients with chronic myelogenous leukemia in chronic phase.

International Journal of Hematology — Sat, 27 Feb 2010 00:00:00 +0100

We present two patients with chronic myelogenous leukemia in whom, following the development of symptomatic pleural effusion, medications were safely switched from dasatinib to nilotinib after a 1-month off-drug period. The lymphocytosis and increased large granular lymphocyte count observed during dasatinib treatment also subsided after switching medications. PMID: 20191333 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria.

International Journal of Hematology — Sat, 27 Feb 2010 00:00:00 +0100

Authors: Wadleigh M, Tefferi A The myeloproliferative neoplasms (MPNs) were first recognized by William Dameshek in 1951. The classic MPNs were polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia. They were originally grouped together based on their shared phenotype of myeloproliferation. Since then, important discoveries have been made, identifying a central role of protein tyrosine kinases in the pathogenesis of these disorders. As such, the 2008 WHO diagnostic classification for myeloproliferative neoplasms has incorporated molecular markers with histologic, clinical and laboratory information into the diagnostic algorithms for the MPNs. Important changes include (1) the change of nomenclature of myeloproliferative dis...

Detection of Drug-Resistant Clones in Chronic Myelogenous Leukemia Patients during Dasatinib and Nilotinib Treatment [Brief Communications]

Clinical Chemistry — Fri, 26 Feb 2010 20:02:00 +0100

Conclusions: These single-step, closed-tube assays specifically target mutations associated with resistance to dasatinib or nilotinib. Compared with standard genotyping, such biased genotyping improves the detection of resistance or alternative features via quantitative analysis of the absolute amount of resistance. (Source: Clinical Chemistry)

Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort

BMJ Online First — Fri, 26 Feb 2010 00:05:31 +0100

Objective The presence of the retrovirus xenotropic murine leukaemia virus-related virus (XMRV) has been reported in peripheral blood mononuclear cells of patients with chronic fatigue syndrome.... (Source: BMJ Online First)

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Emergence of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term imatinib mesylate treatment

Blood — Thu, 25 Feb 2010 17:22:40 +0100

Imatinib mesylate has been demonstrated to allow the emergence of T cells directed against chronic myeloid leukemia cells. A total of 10 Philadelphia chromosome–positive acute lymphoblastic leukemia patients receiving high-dose imatinib mesylate maintenance underwent long-term immunological monitoring (range, 2-65 months) of p190BCR-ABL–specific T cells in the bone marrow and peripheral blood. p190BCR-ABL–specific T lymphocytes were detected in all patients, more frequently in bone marrow than in peripheral blood samples (67% vs 25%, P < .01) and resulted significantly associated with lower minimal residual disease values (P < .001), whereas absent at leukemia relapse. Specific T cells were mainly effector memory CD8+ and CD4+ T cells, producing interferon-, tumor n...

A novel Rag2-/-{gamma}c-/--xenograft model of human CLL

Blood — Thu, 25 Feb 2010 17:22:40 +0100

Easily reproducible animal models that allow for study of the biology of chronic lymphocytic leukemia (CLL) and to test new therapeutic agents have been very difficult to establish. We have developed a novel transplantable xenograft murine model of CLL by engrafting the CLL cell line MEC1 into Rag2–/–c–/– mice. These mice lack B, T, and natural killer (NK) cells, and, in contrast to nude mice that retain NK cells, appear to be optimal recipient for MEC1 cells, which were successfully transplanted through either subcutaneous or intravenous routes. The result is a novel in vivo model that has systemic involvement, develops very rapidly, allows the measurement of tumor burden, and has 100% engraftment efficiency. This model closely resembles aggressive human CLL and co...

A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers

BioMed Central — Thu, 25 Feb 2010 00:00:00 +0100

Background: Genetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies. Results: Here we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of greater than or equal to 25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs T-ALL. For majority of the genes expression could be restored in methylated ...

Membranoproliferative Glomerulonephritis Secondary to Monoclonal Gammopathy.

Clinical Journal of the American Society of Nephrology : CJASN — Thu, 25 Feb 2010 00:00:00 +0100

CONCLUSIONS: Monoclonal gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal gammopathy. PMID: 20185597 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

Merkel Cell Carcinoma in the Peripheral Blood of a Patient With Concomitant Chronic Lymphocytic Leukemia and Multiple Myeloma [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:03 +0100

(Source: Journal of Clinical Oncology)

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Targeting Chronic Myeloid Leukemia Stem Cells

Current Hematologic Malignancy Reports — Wed, 24 Feb 2010 06:55:53 +0100

Abstract Chronic myeloid leukemia (CML) arises as a consequence of a chromosomal translocation giving rise to the Philadelphia chromosome and Bcr-Abl oncogene. CML is a clonal disease of stem cell origin and an excellent example of a malignancy in which tumor-initiating cells may hold the key to disease eradication. The known molecular basis of CML has enabled the development of Abl-specific tyrosine kinase inhibitors, such as imatinib mesylate. However, the success of tyrosine kinase inhibitors, as rationally designed first-line therapies, has been tempered by problems of disease persistence and resistance. Residual disease has been shown to be enriched within the stem cell compartment and to persist at stable levels for up to 5 years of complete cytogenetic response...

Phase IV study evaluating efficacy of escalated dose of imatinib in chronic myeloid leukemia patients showing suboptimal response to standard dose imatinib

Annals of Hematology — Wed, 24 Feb 2010 06:47:46 +0100

In conclusion, escalated dose imatinib shows considerable efficacy with tolerable toxicity in CML patients showing suboptimal response to standard dose imatinib. EMR is an early predictive marker for positive imatinib response. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00277-010-0910-8Authors Youngil Koh, Seoul National University Hospital Department of Internal Medicine 28 Yongon-dong, Jongno-gu Seoul 110-744 Republic of KoreaInho Kim, Seoul National University Hospital Department of Internal Medicine 28 Yongon-dong, Jongno-gu Seoul 110-744 Republic of KoreaSung-Soo Yoon, Seoul National University Hospital Department of Internal Medicine 28 Yongon-dong, Jongno-gu Seoul 110-744 Republic of KoreaByoung Kook Kim, Seoul National University Hospital Department ...

RNA quantification using gold nanoprobes - application to cancer diagnostics

Journal of Nanobiotechnology — Wed, 24 Feb 2010 00:00:00 +0100

Molecular nanodiagnostics applied to cancer may provide rapid and sensitive detection of cancer related molecular alterations, which would enable early detection even when those alterations occur only in a small percentage of cells. The use of gold nanoparticles derivatized with thiol modified oligonucleotides (Au-nanoprobes) for the detection of specific nucleic acid targets has been gaining momentum as an alternative to more traditional methodologies. Here, we present an Au-nanoparticles based approach for the molecular recognition and quantification of the BCR-ABL fusion transcript (mRNA), which is responsible for chronic myeloid leukemia (CML), and to the best of our knowledge it is the first time quantification of a specific mRNA directly in cancer cells is reported. This inexpensive ...

Pentostatin and rituximab therapy for previously untreated patients with B-cell chronic lymphocytic leukemia

Cancer — Wed, 24 Feb 2010 00:00:00 +0100

The combination of pentostatin (P), cyclophosphamide (C), and rituximab (R) achieved an overall response (OR) rate >90%, with >40% complete responses (CRs) in patients with untreated chronic lymphocytic leukemia (CLL).To evaluate whether the tolerability of this regimen could be enhanced without sacrificing efficacy, a phase 2 trial was conducted of P and R without C, using a higher P dose (4 mg/m2). Among the 33 patients enrolled, 82% were male, the median age was 65 years (9 patients were aged [ge]70 years), and 64% were classified as having Rai stage III to IV disease.The OR rate was 76%, with 9 CRs (27%), 5 nodular partial responses, and 11 partial responses (PRs) reported. At the time of last follow-up, 29 of 33 patients were still alive at a median follow-up of 14 months (range, 1-34...

Further doubt cast on virus link to chronic fatigue syndrome

ScienceDaily Headlines — Tue, 23 Feb 2010 16:26:20 +0100

Researchers investigating UK samples have found no association between the controversial xenotropic murine leukemia virus-related virus and chronic fatigue syndrome. Their study calls into question a potential link described late last year by an American research team. (Source: ScienceDaily Headlines)

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Allogenic bone marrow transplantation with fludarabine/busulfan16 conditioning regimen and dasatinib maintenance therapy for elderly Philadelphia-positive acute/advanced leukemia patients

Leukemia Research — Tue, 23 Feb 2010 14:33:41 +0100

Therapeutic outcome of chronic myelogenous leukemia (CML) in advanced phases and of Philadelphia chromosome-positive (Ph+) acute leukemias remains dismal, even with tyrosine kinase inhibitors (TKIs) against Bcr-Abl or hematopoietic stem cell transplantation (HSCT) with maximally myeloablative conditioning (MAST). Especially, because patients over 55 years old are not eligible for MAST, the establishment of a treatment strategy for elderly patients with acute/advanced Ph+ leukemias has long been anticipated. We here present our experience with the use of fludarabine (Flu)/busulfan (Bu) 16 conditioning regimen (FB16) and dasatinib maintenance therapy following allogenic bone marrow transplantation (BMT) for two elderly patients with Ph+ acute/advanced leukemia. (Source: Leukemia Research)

Isolated CNS relapse of CML after bone marrow transplantation

Leukemia Research — Tue, 23 Feb 2010 14:33:41 +0100

Isolated extramedullary relapse (EMR) of chronic myelogenous leukemia (CML) after bone marrow transplantation (BMT) is rare, seen in only 0.21% of cases . EMR in the central nervous system (CNS) is a rare event, and when seen is more commonly associated with lymphoblastic cells . Only two cases of CNS myeloblastic relapse have been reported previously . To our knowledge, isolated CNS myeloid blastic crisis after allogenic BMT for CML has previously not been reported. (Source: Leukemia Research)

Chronic lymphocytic leukemia presenting with symptomatic peritoneal infiltration

Leukemia Research — Tue, 23 Feb 2010 14:33:41 +0100

We report the very rare case of CLL diagnosis in a patient suffering from epigastralgia due to peritoneal infiltration. (Source: Leukemia Research)

Major molecular response achieved with dasatinib in a CML patient with F317L BCR-ABL kinase domain mutation

Leukemia Research — Tue, 23 Feb 2010 14:33:40 +0100

We describe a CML patient in chronic phase with F317L mutation who achieved and maintained a complete cytogenetic and a major molecular response on dasatinib treatment. (Source: Leukemia Research)

A thrombocytosis occurring in Philadelphia positive CML in molecular response to imatinib can reveal an underlying JAK2V617F myeloproliferative neoplasm

Leukemia Research — Tue, 23 Feb 2010 14:33:40 +0100

We report here two new cases of JAK2V617F mutation discovered in Ph+ CML patients under imatinib treatment and compare our findings with those of similar reports. (Source: Leukemia Research)

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Chronic myeloid leukemia: A disease of youth in Brazil

Leukemia Research — Tue, 23 Feb 2010 14:33:39 +0100

Chronic myeloid leukemia (CML) is usually an insidious disease and the median age at diagnosis is stated in Hematology text books to be around 50 years. In the past, patients seek medical attention as a consequence of symptoms of vigorous hematopoiesis (fever, sweats, bone pain, weight loss, and fatigue) or signs of extramedullary hematopoiesis (splenomegaly and left upper quadrant discomfort). However, current medical practice and the periodic routine medical evaluation resulted in shifts in clinicohematologic picture and it is becoming more common for patients to be diagnosed before the development of symptoms . Considering such shift, it was expected that average age at diagnosis could be younger. However, the age was significantly lower in interferon studies than in recent imatinib mes...

Analyses on clinical characteristic and prognoses of 41 patients with chronic myelomonocytic leukemia in China

Leukemia Research — Tue, 23 Feb 2010 14:33:37 +0100

Abstract: Purpose: To investigate clinical characteristic and prognostic factors for chronic myelomonocytic leukemia (CMML).Methods: A retrospective cohort study was used in the research. We investigated clinical and laboratory characteristics of CMML patients and survival status. Patients were followed up regularly through out the course of the research.Results: Forty-one cases were diagnosed as CMML, including 27 male and 14 female patients. Median WBC was 13.7×109/L. Five patients had leukocytopenia (1.92–3.46×109/L). Median monocyte count in the peripheral blood was 2.13×109/L. All patients presented with bone marrow dysplasia, and most showed hyperplasia, except 3 cases. Abnormal chromosome was detected in 34% cases. Median survival time for CMML-1 and CMML-2 was 20 and 12 months...

Pediatric acute lymphoblastic leukemia: There is no TEL-ing what wonders lie ahead

Leukemia Research — Tue, 23 Feb 2010 14:33:36 +0100

The advent of molecular medicine has allowed physicians and scientists to decipher some of nature's mysteries. Few stories are more exhilarating than that of the successes in pediatric acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML). Indeed, children with ALL are now curable without the need for cranial radiation and imatinib mesylate has changed the landscape of CML therapy . Despite these advances disease recurrence and adverse late effects continue to dampen our celebrations. Enticing dormant cancer stem cells to undergo mitosis and offering risk-directed therapy are current endeavors aimed to overcome these obstacles. (Source: Leukemia Research)

Right and left shifts for age in MDS

Leukemia Research — Tue, 23 Feb 2010 14:33:35 +0100

Myelodysplasia is a Greek word meaning “morphological abnormality of the marrow” and may be seen in different disorders including autoimmune/infective/chronic diseases, megaloblastic anemias, and toxic susbstance exposure. For this reason myelodysplasia requires a long list of differential diagnoses. The myelodysplastic syndrome (MDS) diagnosis is based on the exclusion of other disorders and is characterized by ineffective hematopoiesis, quantitative/qualitative cellular defects and moderate risk of leukemic transformation. Abnormal differentiation/maturation of myeloid cells, bone marrow failure and genetic instability are the hallmarks of this heterogenous entity. In clinical practice the first step is to differentiate myelodysplasia from MDS. Diagnosis of MDS requires a team of exp...

Mathematical Model Gives New Hope To Chronic Myeloid Leukaemia Patients

Health News from Medical News Today — Tue, 23 Feb 2010 09:00:00 +0100

Doctors can now understand better chronic myeloid leukaemia (CML), including how it responds to therapy, thanks to a new mathematical model for the disease, developed by scientists in Portugal, Belgium and the United States. The work, to be published in the June edition of the journal Haematologica, also reveals that current therapies which are not believed to cure CML with the right protocol can actually get rid of the disease, and provides guidelines on how to do that. CML although rare, because of effective life-extending therapies, is now one of the most common leukaemias in the world... (Source: Health News from Medical News Today)

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Mathematical Model Gives New Hope To Chronic Myeloid Leukaemia Patients

Lymphoma / Leukemia News From Medical News Today — Tue, 23 Feb 2010 09:00:00 +0100

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

World Pharma News — Tue, 23 Feb 2010 00:00:00 +0100

Bone marrow mesenchymal stromal cells non-selectively protect chronic myeloid leukemia cells from imatinib-induced apoptosis via the CXCR4/CXCL12 axis.

Haematologica — Tue, 23 Feb 2010 00:00:00 +0100

Conclusions Human MSC mediate protection of CML cells from imatinib-induced apoptosis. Disruption of CXCL12/CXCR4 axis at least in part restores sensitivity to imatinib. The combination of anti-CXCR4 antagonists with TK inhibitors may represent a powerful approach in the treatment of CML. PMID: 20179085 [PubMed - as supplied by publisher] (Source: Haematologica)

Rituxan Approved for Chronic Lymphocytic Leukemia

MedicineNet Allergies General — Mon, 22 Feb 2010 07:00:00 +0100

Title: Rituxan Approved for Chronic Lymphocytic LeukemiaCategory: Health NewsCreated: 2/19/2010 12:10:00 PMLast Editorial Review: 2/22/2010 (Source: MedicineNet Allergies General)

Rituxan Approved for Chronic Lymphocytic Leukemia

MedicineNet Cancer General — Mon, 22 Feb 2010 07:00:00 +0100

Title: Rituxan Approved for Chronic Lymphocytic LeukemiaCategory: Health NewsCreated: 2/19/2010 12:10:00 PMLast Editorial Review: 2/22/2010 (Source: MedicineNet Cancer General)

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Rituxan Approved for Chronic Lymphocytic Leukemia

MedicineNet Skin General — Mon, 22 Feb 2010 07:00:00 +0100

Title: Rituxan Approved for Chronic Lymphocytic LeukemiaCategory: Health NewsCreated: 2/19/2010 12:10:00 PMLast Editorial Review: 2/22/2010 (Source: MedicineNet Skin General)

Expression of the leukemic prognostic marker CD7 is linked to epigenetic modifications in chronic myeloid leukemia

Molecular Cancer — Mon, 22 Feb 2010 00:00:00 +0100

Conclusion: These findings indicate a link between epigenetic modifications and CD7 expression in primitive CML cells. (Source: Molecular Cancer)

Rituximab for the Treatment of Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukaemia

Drugs — Sat, 20 Feb 2010 14:12:41 +0100

(Source: Drugs)

Novartis Drug Tasigna® Receives FDA Priority Review For Newly Diagnosed Patients With Early-stage Chronic Myeloid Leukemia

Health News from Medical News Today — Sat, 20 Feb 2010 10:00:00 +0100

Novartis announced that Tasigna® (nilotinib) has been granted priority review by the US Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. FDA priority review status is granted to therapies that offer major advances in treatment or provide a treatment where no adequate therapy exists. This status accelerates the standard review time from 10 to six months... (Source: Health News from Medical News Today)

US FDA Approves Rituxan/MabThera For The Most Common Type Of Adult Leukemia

Health News from Medical News Today — Sat, 20 Feb 2010 10:00:00 +0100

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the US Food and Drug Administration (FDA) approved Rituxan/MabThera (rituximab) plus fludarabine and cyclophosphamide (FC) chemotherapy for people with either previously untreated (first-line) or previously treated (relapsed or refractory) CD20-positive chronic lymphocytic leukemia (CLL). CLL is the most common type of leukemia in adults, accounting for approximately 30-40% of all forms of leukemia in Western countries. Overall incidence of CLL is around four per 100,000 and is 50% more common in men than in women1... (Source: Health News from Medical News Today)

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Novartis Drug Tasigna® Receives FDA Priority Review For Newly Diagnosed Patients With Early-stage Chronic Myeloid Leukemia

Lymphoma / Leukemia News From Medical News Today — Sat, 20 Feb 2010 10:00:00 +0100

US FDA Approves Rituxan/MabThera For The Most Common Type Of Adult Leukemia

Lymphoma / Leukemia News From Medical News Today — Sat, 20 Feb 2010 10:00:00 +0100

Novartis Drug Tasigna(R) Receives FDA Priority Review For Newly Diagnosed Patients With Early-Stage Chronic Myeloid Leukemia

Health News from Medical News Today — Sat, 20 Feb 2010 09:00:00 +0100

Novartis announced that Tasigna® (nilotinib) 200 mg capsules has been granted priority review by the US Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. FDA priority review status is granted to therapies that offer major advances in treatment or provide a treatment where no adequate therapy exists. This status accelerates the standard review time from 10 to six months... (Source: Health News from Medical News Today)

Novartis Drug Tasigna(R) Receives FDA Priority Review For Newly Diagnosed Patients With Early-Stage Chronic Myeloid Leukemia

Lymphoma / Leukemia News From Medical News Today — Sat, 20 Feb 2010 09:00:00 +0100

FDA Approves Rituxan Plus Chemotherapy For The Most Common Type Of Adult Leukemia

Health News from Medical News Today — Sat, 20 Feb 2010 01:00:00 +0100

Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), and Biogen Idec (Nasdaq: BIIB) announced today the U.S. Food and Drug Administration (FDA) approved Rituxan® (rituximab) in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL). CLL is the most common form of adult leukemia and is a slow growing cancer that occurs when abnormal or malignant white blood cells are found in the blood and bone marrow... (Source: Health News from Medical News Today)

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FDA Approves Rituxan Plus Chemotherapy For The Most Common Type Of Adult Leukemia

Cancer / Oncology News From Medical News Today — Sat, 20 Feb 2010 01:00:00 +0100

Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), and Biogen Idec (Nasdaq: BIIB) announced today the U.S. Food and Drug Administration (FDA) approved Rituxan® (rituximab) in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL)... (Source: Cancer / Oncology News From Medical News Today)

FDA Approves Rituxan to Treat Chronic Lymphocytic Leukemia

MedlinePlus Health News — Fri, 19 Feb 2010 22:55:32 +0100

Source: Food and Drug Administration Related MedlinePlus Topic: Leukemia, Adult Chronic (Source: MedlinePlus Health News)

FDA approves Rituxan for form of leukemia

bizjournals.com Health Care:Biotechnology headlines — Fri, 19 Feb 2010 19:37:15 +0100

Regulators approved the use of the Genentech Inc. and Biogen Idec treatment Rituxan as part of a combination therapy for chronic lymphocytic leukemia. (Source: bizjournals.com Health Care:Biotechnology headlines)

FDA Approves Rituximab for Chronic Lymphocytic Leukemia

Medscape Medical News Headlines — Fri, 19 Feb 2010 17:09:14 +0100

The FDA has approved a new indication for rituximab injection for the treatment of patients with newly diagnosed or relapsed CD20-positive chronic lymphocytic leukemia. Medscape Medical News (Source: Medscape Medical News Headlines)

Reduction of Raf Kinase Inhibitor Protein Expression by Bcr-Abl Contributes to Chronic Myelogenous Leukemia Proliferation [Signal Transduction]

Journal of Biological Chemistry — Fri, 19 Feb 2010 14:39:19 +0100

Chronic myelogenous leukemia (CML) is characterized by a reciprocal chromosomal translocation (9;22) that generates the Bcr-Abl fusion gene. The Ras/Raf-1/MEK/ERK pathway is constitutively activated in Bcr-Abl-transformed cells, and Ras activity enhances the oncogenic ability of Bcr-Abl. However, the mechanism by which Bcr-Abl activates the Ras pathway is not completely understood. Raf kinase inhibitor protein (RKIP) inhibits activation of MEK by Raf-1 and its downstream signal transduction, resulting in blocking the MAP kinase pathway. In the present study, we found that RKIP was depleted in CML cells. We investigated the interaction between RKIP and Bcr-Abl in CML cell lines and Bcr-Abl+ progenitor cells from CML patients. The Abl kinase inhibitors and depletion of Bcr-Abl induced the ex...

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Novartis Drug Tasigna(R) Receives FDA Priority Review for Newly Diagnosed Patients With Early-Stage Chronic Myeloid Leukemia

HSMN NewsFeed — Fri, 19 Feb 2010 14:00:01 +0100

EAST HANOVER, N.J., Feb. 19 (HSMN NewsFeed) -- Novartis announced today that Tasigna® (nilotinib) 200 mg capsules has been granted priority review by the US Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed P... Biopharmaceuticals, OncologyNovartis, Tasigna, nilotinib, Ph+ CML (Source: HSMN NewsFeed)

FDA Adds to CLL Weapons

MedPage Today Hematology/Oncology — Fri, 19 Feb 2010 13:13:05 +0100

WASHINGTON (MedPage Today) -- The FDA has approved rituximab (Rituxan) for treatment of patients with previously untreated chronic lymphocytic leukemia (CLL) or with CLL that has failed prior therapy. (Source: MedPage Today Hematology/Oncology)

FDA Approves Rituxan to Treat Chronic Lymphocytic Leukemia

Drugs.com - New Drug Approvals — Fri, 19 Feb 2010 12:35:07 +0100

ROCKVILLE, Md., Feb. 18, 2010--The U.S. Food and Drug Administration today approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. Rituxan, an anti-cancer... (Source: Drugs.com - New Drug Approvals)

FDA Approves Rituxan To Treat Chronic Lymphocytic Leukemia

Lymphoma / Leukemia News From Medical News Today — Fri, 19 Feb 2010 11:00:00 +0100

The U.S. Food and Drug Administration approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. Rituxan, an anti-cancer drug, is intended for patients with CLL who are beginning chemotherapy for the first time and for those who have not responded to other cancer drugs for CLL... (Source: Lymphoma / Leukemia News From Medical News Today)

FDA Approves Rituxan To Treat Chronic Lymphocytic Leukemia

Health News from Medical News Today — Fri, 19 Feb 2010 11:00:00 +0100

The U.S. Food and Drug Administration approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. Rituxan, an anti-cancer drug, is intended for patients with CLL who are beginning chemotherapy for the first time and for those who have not responded to other cancer drugs for CLL. Rituxan is administered with two other chemotherapy drugs, fludarabine and cyclophosphamide... (Source: Health News from Medical News Today)

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The uncontrolled clinical trial: scientific, ethical, and practical reasons for being

Internal and Emergency Medicine — Fri, 19 Feb 2010 06:44:39 +0100

Abstract According to principles of clinical trial design, the demonstration of efficacy of a new treatment is based on comparing the response in the treated group with that of a control group receiving placebo or another active treatment. The need for a control group is also recommended by the major international institutions that govern the ethics and the practice of clinical research. Despite these principles and recommendations, inspection of a purposive sample of ongoing clinical trials listed in the NIH registry (http://ClinicalTrials.gov) reveals that as many as one-third of trials are uncontrolled. Since these trials were approved through a formal evaluation by ethics committees, the lack of adequate control was not perceived as a major deficiency in the study desig...

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Media News — Fri, 19 Feb 2010 06:00:00 +0100

Roche announced today that the US Food and Drug Administration (FDA) approved Rituxan/MabThera (rituximab) plus fludarabine and cyclophosphamide (FC) chemotherapy for people with either previously untreated (first-line) or previously treated (relapsed or refractory) CD20-positive chronic lymphocytic leukemia (CLL). (Source: Roche Media News)

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Investor Update — Fri, 19 Feb 2010 06:00:00 +0100

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Media News — Fri, 19 Feb 2010 06:00:00 +0100

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Investor Update — Fri, 19 Feb 2010 06:00:00 +0100

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Rituxan Approved for Chronic Lymphocytic Leukemia

Modern Medicine — Fri, 19 Feb 2010 00:00:00 +0100

(Source: Modern Medicine)

Life Expectancy in Patients Surviving More Than 5 Years After Hematopoietic Cell Transplantation [Hematologic Malignancies]

Journal of Clinical Oncology — Thu, 18 Feb 2010 23:00:38 +0100

Conclusion Patients who have survived for at least 5 years after hematopoietic cell transplantation without recurrence of the original disease have a high probability of surviving for an additional 15 years, but life expectancy is not fully restored. Further effort is needed to reduce the burden of disease and treatment-related complications in this population. (Source: Journal of Clinical Oncology)

FDA Approves Rituxan to Treat Chronic Lymphocytic Leukemia

Food and Drug Administration — Thu, 18 Feb 2010 22:06:00 +0100

The U.S. Food and Drug Administration today approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. (Source: Food and Drug Administration)

New Opportunities to Treat the T315I-Bcr-Abl Mutant in Chronic Myeloid Leukaemia: Tyrosine Kinase Inhibitors and Molecules that Act by Alternative Mechanisms.

Current Medicinal Chemistry — Thu, 18 Feb 2010 00:00:00 +0100

Authors: Schenone S, Brullo C, Botta M Resistance to the Bcr-Abl inhibitors approved for the treatment of chronic myeloid leukaemia (CML) may arise from different mechanisms, including Bcr-Abl amino acid mutations, gene amplification and mechanisms independent of Bcr-Abl. The T315I mutation at the gatekeeper residue is very frequent in advanced phases of the disease and is one of the main causes of resistance, disrupting important contact points between the inhibitors and the enzyme. Different strategies have been implemented to overcome this resistance, including the synthesis of new Bcr-Abl ATPcompetitive or non-ATP-competitive inhibitors, dual Aurora/Bcr-Abl inhibitors and multi-targeted kinase inhibitors. An alternative approach is the use of other compounds that do not bind direct...

Identification of circulatory and excretory metabolites of meisoindigo in rat plasma, urine and feces by high-performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry.

Rapid Communications in Mass Spectrometry : RCM — Thu, 18 Feb 2010 00:00:00 +0100

In this study, in vivo circulatory metabolites of meisoindigo in rat plasma, as well as excretory metabolites in rat urine and feces, were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Integration of multiple reaction monitoring with conventional metabolic profiling methodology was adopted to enable a more sensitive detection of in vivo metabolites. By comparing with the MS/MS spectra and retention times of the in vitro reduced metabolites, the major metabolites in rat plasma were proposed to form from 3,3' double bond reduction, whereas the minor metabolites were formed from reduction followed by N-demethylation, and reduction followed by phenyl mono-oxidation. The major metabolites in the rat urine were proposed to form from reduction followed by phenyl mono-ox...

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Eponym

European Journal of Pediatrics — Wed, 17 Feb 2010 18:27:59 +0100

Abstract Rolf Kostmann (1909–1982) was a Swedish pediatrician and army doctor. He was the first to describe an inherited form of chronic neutropenia in childhood. In 1956, Kostmann published his article “Infantile genetic agranulocytosis” in Acta Paediatrica. “Infantile agranulocytosis,” as Rolf Kostmann named this hereditary syndrome, has been known for more than half a century, yet the underlying genetic mutations have remained unknown for many decades. Fifty years later, homozygous mutations in the gene encoding the mitochondrial protein HCLS1-associated X1 were found in affected members of the original Kostmann pedigree. Therefore, the eponym “Kostmann disease” best fits this specific mutation and mode of inheritance. The identification of genetic cause no...

Virus Link To Chronic Fatigue Questioned

Biology / Biochemistry News From Medical News Today — Wed, 17 Feb 2010 13:00:00 +0100

Virus Link To Chronic Fatigue Questioned

Health News from Medical News Today — Wed, 17 Feb 2010 13:00:00 +0100

Researchers investigating UK samples have found no association between the controversial xenotropic murine leukaemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). Their study, published in BioMed Central's open access journal Retrovirology, calls into question a potential link described late last year by an American research team. Kate Bishop from the MRC National Institute for Medical Research worked with a team of researchers to test blood and serum samples from 170 CFS patients and 395 healthy controls, using quantitative PCR and a virus neutralization assay... (Source: Health News from Medical News Today)

Electrochemical biosensor based on nanogold-modified poly-eriochrome black T film for BCR/ABL fusion gene assay by using hairpin LNA probe.

Talanta — Wed, 17 Feb 2010 08:38:43 +0100

Authors: Lin L, Chen J, Lin Q, Chen W, Chen J, Yao H, Liu A, Lin X, Chen Y A novel electrochemical biosensor is described for detection of breakpoint cluster region gene and a cellular abl (BCR/ABL) fusion gene in chronic myelogenous leukemia (CML) by using thiolated-hairpin locked nucleic acids (LNA) as the capture probe. The hairpin LNA probe was immobilized on the nanogold (NG)/poly-eriochrome black T (EBT) film-modified glassy carbon electrode (GCE). The immobilized LNA probe could selectively hybridize with its target DNA on LNA/NG/EBT/GCE surface. The immobilization and hybridization of the LNA probe were characterized with cyclic voltammetry and electrochemical impedance spectroscopy. The hybridization of the immobilized LNA probe with the target DNA was detected by differential...

The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation

Cancer — Wed, 17 Feb 2010 00:00:00 +0100

Patients with recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) often have chemotherapy-resistant disease, resulting in poor prognosis. The aim of this study was to learn if inhibition of the mammalian target of rapamycin (mTOR) would produce tumor responses.This was a phase 2 study of oral single-agent everolimus (10 mg/day) for recurrent/refractory indolent lymphoid malignancies including CLL.Four of 22 patients with CLL (18%; 95% confidence interval, 5%-40%) achieved a partial remission to therapy. An unanticipated finding in this study was an increase in absolute lymphocyte count (ALC) associated with a decrease in lymphadenopathy in 8 (36%) patients. ALC increased a median of 4.8-fold (range, 1.9- to 25.1-fold), and the clinically measurable lymphadeno...

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Circulating endothelial cells in patients with chronic lymphocytic leukemia

Cancer — Wed, 17 Feb 2010 00:00:00 +0100

In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain.In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition, CECs were characterized by immunophenotypic, fluorescence in situ hybridization (FISH), and gene expression profile analyses.In patients with CLL, CECs were increased compared with controls. A higher level of CECs (>20/[mu]L) identified a subset of patients with a more aggressive disease course characterized by a shorter time to first treatment both in univariate and multivariate analyses. In FISH analysis, 7 patients...

Further doubt cast on virus link to chronic fatigue

EurekAlert! - Social and Behavioral Science — Tue, 16 Feb 2010 05:00:00 +0100

(BioMed Central) Researchers investigating UK samples have found no association between the controversial xenotropic murine leukemia virus-related virus and chronic fatigue syndrome. Their study, published in BioMed Central's open access journal Retrovirology, calls into question a potential link described late last year by an American research team. (Source: EurekAlert! - Social and Behavioral Science)

Matrix Metalloproteinase-9 Promotes Chronic Lymphocytic Leukemia B Cell Survival through Its Hemopexin Domain

Cancer Cell — Tue, 16 Feb 2010 04:00:09 +0100

Javier Redondo-Muñoz, Estefanía Ugarte-Berzal, María José Terol, Philippe E. Van den Steen, Mercedes Hernández del Cerro, Martin Roderfeld, Elke Roeb, Ghislain Opdenakker, José A. García-Marco, Angeles García-Pardo. Matrix metalloproteinase-9 (MMP-9) is the major MMP produced by B-CLL cells and contributes to their tissue infiltration by degrading extracellular and membrane-anchored substrates. Here we descri.... (Source: Cancer Cell)

The Bcl-2 Family as a Rational Target for the Treatment of B-Cell Chronic Lymphocytic Leukaemia.

Current Medicinal Chemistry — Tue, 16 Feb 2010 00:00:00 +0100

Authors: Capitani N, Baldari CT B-cell chronic lymphocytic leukaemia (B-CLL) is the most common lymphoid malignancy in the Western world, characterized by clonal growth and accumulation of monoclonal CD5+ B-cells in peripheral blood, bone marrow and peripheral lymphoid organs. Although the clinical course in B-CLL patients is highly variable, the most conserved feature is the prolonged survival of malignant B-cells, which has been associated to defects in the apoptotic machinery. The apoptosis defects are mainly determined by a defective balance among pro- and anti-apoptotic members of the Bcl-2 family, often related to resistance of CLL B-cells to chemotherapy. Purine nucleoside analogs or alkylating agents, alone or in combination, are the first-line treatment for B-CLL patients. Alt...