J Natl Compr Canc Netw. 2005 Nov ; 3(6): 757-68
Imatinib, a specific small molecule inhibitor of the Abl kinase, has become the standard drug therapy for chronic myelogenous leukemia in all phases. More than 80% of newly diagnosed patients with chronic phase attain a complete cytogenetic response (CCR). Although remissions in patients with early disease are generally durable, acquired resistance after an initial response is common in advanced disease. Reactivation of Bcr-Abl signaling is almost invariably present at the time of relapse, consistent with re-establishment of the initial pathogenetic mechanism. Mutations in the kinase domain (KD) of Bcr-Abl that impair drug binding and increased _expression_ of Bcr-Abl have been identified as major mechanism of acquired drug resistance. The fact that Bcr-Abl remains central to disease pathogenesis at the time of relapse implies that it also remains the optimal drug target.
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Posted by Rob to CML Newswire: Medical And Technical News On Chronic Myelogenous Leukemia at 12/17/2005 04:57:22 PM
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