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    Association details:
    Biomarker:BCR-ABL1 F317L
    Cancer:Chronic Myeloid Leukemia
    Drug:dasatinib (c-KIT inhibitor, Bcr-abl tyrosine kinase inhibitor, Src kinase inhibitor, EphA2 receptor antagonist, PDGFR β antagonist) +
    imatinib (c-KIT inhibitor, Bcr-abl tyrosine kinase inhibitor, PDGFR inhibitor)
    Direction:Resistant
    Evidence:
    Evidence Level:
    Resistant: D – Preclinical
    New
    Source:
    Proc Natl Acad Sci U S A
    Title:

    Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance

    Excerpt:
    To examine the potential role of conformational binding properties in drug resistance, we mapped the mutations in BCR-ABL capable of conferring resistance to BMS-354825...Of note, these three mutants were the most frequently recovered in our screen. L248R, E255K, F317L, and the previously uncharacterized mutant V299L show modest changes in IC50, increasing ≈10- to 15-fold from WT BCR-ABL...IC50 for growth of Ba/F3 stable lines grown in the presence of BMS-354825 and imatinib.
    DOI:
    10.1073/pnas.0409770102