Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia
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چکیده
منابع مشابه
FLT3 inhibition as tailored therapy for acute myeloid leukemia.
dum-Nielsen K. Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8. Leukemia 2002;16:1390-3. 44. Cashman J, Henkelman D, Humphries K, Eaves C, Eaves A. Individual BFU-E in polycythemia vera produce both erythropoietin dependent and independent progeny. Blood 1983;61:876-84. 45. Levin J, Cocault L, Demerens C, Challier C, Pauchard...
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Acute myeloid leukemia (AML) remains a serious unmet medical need. Despite high remission rates with chemotherapy standard-of-care treatment, the disease eventually relapses in a major proportion of patients. Activating Fms-like tyrosine kinase 3 (FLT3) mutations are found in approximately 30% of patients with AML. Targeting FLT3 receptor tyrosine kinase has shown encouraging results in treatin...
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Activating mutations in FLT3 confer poor prognosis for individuals with acute myeloid leukemia (AML). Clinically active investigational FLT3 inhibitors can achieve complete remissions but their utility has been hampered by acquired resistance and myelosuppression attributed to a 'synthetic lethal toxicity' arising from simultaneous inhibition of FLT3 and KIT. We report a novel chemical strategy...
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P27 Kip1 (p27) can prevent cell proliferation by inactivating cyclin-dependent kinases. This function is impaired upon phosphorylation of p27 at tyrosine residue 88. We observed that FLT3 and FLT3-ITD can directly bind and selectively phosphorylate p27 on this residue. Inhibition of FLT3-ITD in cell lines strongly reduced p27 tyrosine 88 phosphorylation and resulted in increased p27 levels and ...
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Mer and Flt3 receptor tyrosine kinases have been implicated as therapeutic targets in acute myeloid leukemia (AML). In this manuscript we describe UNC1666, a novel ATP-competitive small molecule tyrosine kinase inhibitor, which potently diminishes Mer and Flt3 phosphorylation in AML. Treatment with UNC1666 mediated biochemical and functional effects in AML cell lines expressing Mer or Flt3 inte...
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ژورنال
عنوان ژورنال: Cancer Cell
سال: 2002
ISSN: 1535-6108
DOI: 10.1016/s1535-6108(02)00080-6