Dasatinib May Override F317L BCR-ABL Kinase Domain Mutation in Patients with Chronic Myeloid Leukemia
Journal Title: Turkish Journal of Hematology - Year 2013, Vol 30, Issue 2
Abstract
To the Editor, The most common mechanisms for resistance in patients with chronic myeloid leukemia (CML) receiving imatinib mesylate are BCR-ABL kinase domain (KD) mutations. The mutations are stratifi ed according to in vitro 50% inhibitory concentration (IC50) values. The F317L KD mutation has been shown to induce a 9- to 13.5-fold increase of dasatinib IC50 with respect to wild-type BCR-ABL in cellular assays [1]. The pharmacokinetic data showed that F317L is predicted to be moderately sensitive to dasatinib [2]. Jabbour et al. [3] published data on a cohort of 20 CML patients with F317L mutation and evaluated the characteristics and outcomes of these patients with tyrosine-kinase inhibitor (TKI) therapy.Among these 20 patients, F317L was detected in 12 after imatinib failure and in 8 after dasatinib failure. In the postimatinib failure group, 3 patients received dasatinib. The best achieved response was partial hematologic response in 1 and complete hematologic response (CHR) in 2. Müller et al. [4] also reported the results of analysis of original dasatinib phase 2/3 trial data according to pre-existing mutations. Of the 402 patients with baseline KD mutations, 14 had F317L mutations; 13 (93%), 2 (14%), and 1 (7%) achieved CHR, major cytogenetic response (MCyR), and complete cytogenetic response (CCyR), respectively. None of the patients achieved major molecular response (MMR).
Authors and Affiliations
Ahmet Eşkazan, Teoman Soysal
Keywords
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- DOI 10.4274/Tjh.2012.0013
- Views 60
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