Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase

Abstract excerpt

Significance One obstacle for the prolonged success of the wonder drug imatinib in leukemia has been the emergence of resistance mutations within the Abl kinase domain. Here, we elucidate the molecular mechanism for resistance of three major mutations in patients treated with imatinib. Unpredictably, the single-site resistance mutations act via a cumulative effect of an only modest decrease in drug affinity,...

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