Posted by rob on April 29, 2009 under Uncategorized | 
Although the BCR/ABL tyrosine kinase inhibitor imatinib is highly effective for treatment of chronic myelogenous leukemia and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia, relapse with emerging imatinib resistance mutations in the BCR/ABL kinase domain poses a significant problem. Here, we show that the multikinase inhibitor sorafenib inhibits proliferation and induces apoptosis at much lower concentrations in Ton.B210 cells when driven by inducibly expressed BCR/ABL than when driven by interleukin-3. The increased sensitivity to sorafenib was also observed in cells inducibly expressing BCR/ABL with the imatinib-resistant E255K or T315I mutation. Sorafenib-induced apoptosis in these cells and Ph+ leukemic cells was synergistically enhanced by rottlerin, bortezo…
Posted by rob on April 24, 2009 under Uncategorized |
Ocular side effects are very common complaints among patients receiving imatinib therapy, with up to 70% of patients experiencing mild to moderate periorbital edema at the doses of 400mg or higher. But the conjunctiva chemosis associated with imatinib mesylate is relatively rare . Here we report that severe conjunctival chemosis secondary to imatinib treatment can be managed by concomitant oral short-term steroid therapy without discontinuation of imatinib. (Source: Leukemia Research)
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In this issue of Leukemia Research, Tavernier-Tardy and colleagues provide evidence that an “adhesive” phenotype of the leukemia cells, characterized by higher surface expression of CXCR4 chemokine receptors, VLA-4 integrins, and the focal adhesion kinase (FAK) is associated with poor outcome in patients with AML. As such, this report is in line with a series of pre-clinical and clinical reports that came out over the last few years (reviewed in ), highlighting the importance of the microenvironment in acute and chronic leukemias. Our current concepts about the microenvironment in leukemia imply that chemokine receptors and adhesion molecules, which normally work hand in hand during leukocyte trafficking , are also central players in leukemia cell migration and homing to tissue niches …
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Posted by rob on April 22, 2009 under Uncategorized |
A population-based cohort was used to determine the incidence and risk factors associated with development of venous thromboembolism (VTE) among Californians diagnosed with acute leukemia between 1993 to 1999. Principal outcomes were deep vein thrombosis in both the lower and upper extremities, pulmonary embolism, and mortality. Among 5394 cases with acute myelogenous leukemia (AML), the 2-year cumulative incidence of VTE was 281 (5.2%). Sixty-four percent of the VTE events occurred within 3 months of AML diagnosis. In AML patients, female sex, older age, number of chronic comorbidities, and presence of a catheter were significant predictors of development of VTE within 1 year. A diagnosis of VTE was not associated with reduced survival in AML patients. Among 2482 cases with acute lymphobl…
Posted by rob on under Uncategorized |
RICHMOND, Va. – A West Virginia widow seeking to link the death of her husband to occupational exposure to herbicides while employed by a tree service failed to link The Dow Chemical Co. and Dow AgroSciences to the chemicals she alleges caused him to contract chronic myelogenous leukemia, and the trial court grant of summary judgment was not in error, a unanimous Fourth Circuit U.S. Court of Appeals panel said April 8 (Melody White, et al v. The Dow Chemical Co., et al., No. 08-1165, 4th Cir.; 2009 U.S. App. LEXIS 7483; See 4/1/05, Page 16).
Full story on lexis.com (Source: LexisNexis® Mealey’s™ Emerging Toxic Torts Legal News)
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Posted by rob on April 20, 2009 under Uncategorized |
Abstract: The purpose of this study was to determine the effect of alemtuzumab on treatment-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DSF) in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) undergoing reduced intensity conditioning (RIC). We compared the outcome of 95 patients treated at the University of Chicago with fludarabine melphalan (Flu + Mel) + alemtuzumab conditioning and 59 patients treated at the M.D. Anderson Cancer Center with Flu + Mel conditioning. Both groups had similar patient and donor characteristics. There were no significant differences in TRM, relapse, survival, and DFS between the 2 groups. The incidence of acute graft-versus-host disease (aGVHD) grade II-IV (relative risk [RR] 5.5, P < .0…
Posted by rob on under Uncategorized |
PORTLAND, OR (MARKET WIRE) MolecularMD Corp, a developer and provider of cancer-based pharmacogenomic diagnostic tests, announced today that it has granted a sub-license agreement for the detection of ABL kinase mutations in Chronic Myelogenous Leukemia (CML) patients to Mayo Foundation for Medical Education and Research (Mayo Clinic). (Source: Market Wire – Pharmaceuticals and Biotech)
Posted by rob on April 15, 2009 under Uncategorized |
Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL–transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL–induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the antileukemic response of IFNs suggest new strategies for immunotherapy of CML. (Source: …
Posted by rob on April 14, 2009 under Uncategorized |
The protein kinase inhibitor imatinib, also known as Gleevec, has been a notable success in treating chronic myelogenous leukemia. A recent paper in BMC Structural Biology reports a 1.75 Å crystal structure of imatinib bound to the oxidoreductase NQO2 and reveals insights into the binding specificity and the off-target effects of the inhibitor. (Source: Journal of Biology)
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Chronic myelogenous leukemia (CML) is one of the myeloproliferative disorders. It accounts for 15[ndash]20% of all leukemias in adults. The mainstay of diagnosis is the detection of Philadelphia chromosome or one of its products. Tyrosine kinase inhibitors changed the paradigm of treating such disease with the good responses. However, they do have side effects. In our case we will report tumor lysis syndrome happening after starting Imatinib myselate. We did a literature review and looked all the cases that documented this complication. (Source: Journal of Clinical Pharmacy and Therapeutics)
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Posted by rob on April 13, 2009 under Uncategorized |
(Source: Proceedings of the National Academy of Sciences)
Posted by rob on April 10, 2009 under Uncategorized |
Posted by rob on April 8, 2009 under Uncategorized |
Posted by rob on under Uncategorized |
Posted by rob on April 4, 2009 under Uncategorized |
