Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain.
نویسندگان
چکیده
The emergence of resistance to the Bcr-Abl inhibitor imatinib mesylate in patients with Philadelphia chromosome-positive (Ph+) leukemia has prompted the development of second-generation compounds active against several imatinib-insensitive mutant forms of Bcr-Abl, including dasatinib (BMS-354825; Bristol-Myers Squibb). In order to assess which pre-existent or emerging kinase domain mutations are associated with decreased clinical efficacy of desatinib, we analyzed BCR-ABL kinase sequences before and during treatment in 21 Ph+ patients who failed to respond to or relapsed during dasatinib therapy. In all patients but one, resistance to dasatinib was invariably found to be associated with mutations at residue 315 and/or at residue 317.
منابع مشابه
Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL.
Resistance to targeted treatment with the BCR-ABL inhibitor, imatinib, in patients with chronic myeloid leukaemia and Philadelphia-positive (Ph+) acute lymphoblastic leukaemia can occur through the selection of point mutations within the ABL kinase domain, which stop imatinib binding without impairing kinase activity. Dasatinib (BMS-354825) is a second-generation tyrosine kinase inhibitor curre...
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ورودعنوان ژورنال:
- Haematologica
دوره 92 3 شماره
صفحات -
تاریخ انتشار 2007