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      BCR-ABL mutant kinetics in CML patients treated with dasatinib.

      Leukemia Research

      administration & dosage, Adult, Thiazoles, Pyrimidines, Protein Kinase Inhibitors, Polymorphism, Restriction Fragment Length, Piperazines, Mutation, Middle Aged, Male, genetics, drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Humans, Fusion Proteins, bcr-abl, Follow-Up Studies, Female, drug effects, Drug Resistance, Neoplasm, Benzamides, Aged

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          Abstract

          Dasatinib is efficient in vitro against most of CML cells harboring ABL kinase domain mutations and induces high rates of response in imatinib-resistant CML patients. Here, we monitored the mutated BCR-ABL transcripts during the follow-up of 12 CML patients treated with dasatinib. We identified four groups of patients based on their sensitivity to dasatinib. Clinical responses were correlated to the in vitro sensitivity of BCR-ABL mutants to dasatinib, however, some discrepancies were observed in a subfraction of CML patients, suggesting subtle differences between in vitro observations and clinical entities and/or the onset of other mechanisms responsible for dasatinib resistance.

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          Journal
          17208297
          10.1016/j.leukres.2006.12.003

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