Dynamic Evolution of Ponatinib Resistant BCR-ABL1 T315 and Compound Mutations

The third-generation tyrosine kinase inhibitor (TKI) ponatinib exhibits activity against all common BCR-ABL1 kinase domain (KD) single mutations, including the highly resistant gatekeeper T315I. However, the drug response is variable and the clinical resistance mutations may still befall with few reports to date. We performed next-generation sequencing (NGS) detection of BCR-ABL1 KD mutations in sequential samples of three BCR-ABL1-positive leukemia patients who developed clinical resistance to ponatinib, to explore the dynamic evolution of ponatinib mutations.