Kinase domain mutants of Bcr enhance Bcr-Abl oncogenic effects
نویسندگان
چکیده
منابع مشابه
Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr.
c-Abl tyrosine kinase is under rigorous control because of an unknown cellular inhibitor that maintains c-Abl in a relatively inactive state. Because SH2 domains are positive regulators of the nonreceptor tyrosine kinases, we tested whether this putative inhibitor would bind to an Abl SH2 protein construct and thus activate the c-Abl tyrosine kinase. Expression of a Mr 10,000 Abl SH2 protein in...
متن کاملresistance remain sensitive to imatinib Several Bcr - Abl kinase domain mutants associated with imatinib mesylate
Imatinib mesylate is a selective Bcr-Abl kinase inhibitor, effective in the treatment of chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses, however, many in blast crisis fail to respond or relapse quickly. Kinase domain mutations are the most commonly identified mechanism associated with relapse. Many of these mutations decrease the sensitivity of the Abl k...
متن کاملSeveral Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib.
Imatinib mesylate is a selective Bcr-Abl kinase inhibitor, effective in the treatment of chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Kinase domain mutations are the most commonly identified mechanism associated with relapse. Many of these mutations decrease the sensitivity of the Abl ...
متن کاملIn vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants.
Imatinib, a Bcr-Abl tyrosine kinase inhibitor, is a highly effective therapy for patients with chronic myelogenous leukemia (CML). Despite durable responses in most chronic phase patients, relapses have been observed and are much more prevalent in patients with advanced disease. The most common mechanism of acquired imatinib resistance has been traced to Bcr-Abl kinase domain mutations with dec...
متن کاملA novel pyridopyrimidine inhibitor of abl kinase is a picomolar inhibitor of Bcr-abl-driven K562 cells and is effective against STI571-resistant Bcr-abl mutants.
Inhibition of the constitutively active Bcr-abl tyrosine kinase(TK) by STI571 has proven to be a highly effective treatment for chronic myelogenous leukemia (CML). However, STI571 is only transiently effective in blast crisis, and drug resistance emerges by amplification of or development of mutational changes in Bcr-abl. We have screened a family of TK inhibitors of the pyrido [2,3-d]pyrimidin...
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ژورنال
عنوان ژورنال: Oncogene
سال: 2007
ISSN: 0950-9232,1476-5594
DOI: 10.1038/sj.onc.1210851