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    Association details:
    Biomarker:FLT3 F691L
    Cancer:Acute Myelogenous Leukemia
    Drug:Iclusig (ponatinib) (Multi-tyrosine kinase inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: D – Preclinical
    New
    Source:
    Blood
    Title:

    Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD

    Excerpt:
    Substitution of the FLT3 “gatekeeper” phenylalanine with leucine (F691L) conferred mild resistance to ponatinib, but substitutions at the FLT3 activation loop (AL) residue D835 conferred a high degree of resistance. Saturation mutagenesis of FLT3-ITD exclusively identified FLT3 AL mutations at positions D835, D839, and Y842....supplemental Figure 1....
    DOI:
    https://dx.doi.org/10.1182%2Fblood-2012-07-442871