Posted by rob on August 28, 2009 under Uncategorized | 
Dasatinib is an oral potent adenosine triphosphate (ATP)–competitive inhibitor of BCR-ABL, cKIT, platelet-derived growth factor receptor, and SRC family kinases (SFKs), which has demonstrated high efficiency in patients with imatinib-resistant chronic myelogenous leukemia. Here, we show that dasatinib weakly affects platelet activation by thrombin or adenosine diphosphate but is a potent inhibitor of platelet signaling and functions initiated by collagen or FcRIIA cross-linking, which require immunoreceptor tyrosine-based activation motif phosphorylation by SFKs. Accordingly, dasatinib treatment rapidly decreases the volume of thrombi formed under arterial flow conditions in whole blood from patients or mice perfused over a matrix of collagen. Moreover, treatment of mice with dasatin…
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Recent advances in the field of immunology in CML are summarized, specifically those in tumor antigen discovery that have been incorporated into the design of new clinical trials. Cancer Control: Journal of the Moffitt Cancer Center (Source: Medscape Allergy Headlines)
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Authors: Mühlenberg T, Zhang Y, Wagner AJ, Grabellus F, Bradner J, Taeger G, Lang H, Taguchi T, Schuler M, Fletcher JA, Bauer S
Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor A (PDGFRA), and treatment with the tyrosine kinase inhibitor imatinib yields responses in the majority of patients. However, most patients develop secondary resistance, which is associated with a dismal prognosis. Histone deacetylase inhibitors (HDACI) have been shown to enhance imatinib activity in imatinib-resistant chronic myelogenous leukemia. Against this background, we explored whether HDACI might provide an alternative therapeutic strategy to KIT/PDGFRA kinase inhibitors in GIST. Inhibition of cell proliferation by HDAC…
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Clinical roundtable monograph. Treatment selection for myelodysplastic syndrome patients in the community setting.
Clin Adv Hematol Oncol. 2009 Jul;7(7):S1-15
Authors: Silverman LR, Lyons RM, Shammo JM, Scott BL
Myelodysplastic syndromes (MDS) represent a collection of heterogeneous malignant bone marrow stem cell disorders that result in the production of dysplastic and ineffective blood cells. The disease is marked by gradually worsening cytopenias and a variable risk for the eventual transformation to acute myelogenous leukemia (AML). The risk of developing MDS increases with age, and disease onset before 50 years is unusual. Several morphologic subtypes of MDS have been identified. Each of these subtypes has specific prognostic and morphologic and/or cytogenetic features which make it unique. The International Prognostic Scoring System (IPSS) was developed to aid in determining the prognosis of patients with MDS; this system categorizes patients into four risk groups for both overall survival and transformation to AML: low, intermediate-1, intermediate-2, and high. The management of MDS is based on the goal of controlling cytopenia-related symptoms, improving survival, improving quality of life, and decreasing risk of progression to AML. Treatment strategies include supportive care, iron chelation, treatment with hematopoietic growth factors,immunosuppressive therapies including lenalidomide, antithymocyte globulin, chemotherapy (eg, azacitidine, decitabine, low-dose Ara-C, 7+3 chemotherapy), and stem cell transplantation. However, selecting the appropriate therapy for each individual patient is critical to optimize clinical benefit. This monograph discusses treatment selection for the MDS patient,including a discussion of the overall survival and maintenance of MDS patients, how an appropriate therapy should be chosen in the community setting, and how MDS classification and risk stratification impacts treatment decisions.
PMID: 19708287 [PubMed - in process]
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Differential methylation pattern of ID4, SFRP1, and SHP1 between acute myeloid leukemia and chronic myeloid leukemia.
J Korean Med Sci. 2009 Jun;24(3):493-7
Authors: Uhm KO, Lee ES, Lee YM, Park JS, Kim SJ, Kim BS, Kim HS, Park SH
To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5′CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.
PMID: 19543515 [PubMed - indexed for MEDLINE]
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Familial occurrence of chronic myeloid leukemia.
Leuk Lymphoma. 2009 May;50(5):854-6
Authors: Caocci G, Atzeni S, Vacca A, Orrù N, Ledda A, La Nasa G
PMID: 19452324 [PubMed - indexed for MEDLINE]
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Dasatinib overcomes imatinib and nilotinib failure in Philadelphia chromosome positive chronic myeloid leukemia with different mechanisms of resistance.
Leuk Lymphoma. 2009 May;50(5):848-50
Authors: Cannella L, Breccia M, Stefanizzi C, Napoleone L, Santopietro M, Alimena G
PMID: 19367499 [PubMed - indexed for MEDLINE]
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