BCR-ABL1 mutations in patients with imatinib-resistant Philadelphia chromosome-positive leukemia by use of the PCR-Invader assay.

BCR-ABL1 kinase domain mutations were evaluated in 60 imatinib-resistant patients with Philadelphia-positive (Ph(+)) leukemia using PCR-Invader assay and direct sequencing. In chronic myelogenous leukemia (CML)--chronic phase (CP), 5 had P-loop mutations and 3 had T315I mutations. CML-CP patients with high Sokal score showed significantly higher incidence of mutations. P-loop mutations were associated with higher risk of disease progression. In CML-advanced phase, P-loop mutations and T315I mutation were associated with significantly shorter survival. In Ph(+) acute lymphoblastic leukemia, overall survival was poor irrespective of mutational status. The PCR-Invader assay is useful for screening of mutations and prediction of prognosis.