ABL1 and chronic myelogenous leukemia, BCR-ABL1 positive: These inhibitors can suppress most clinically relevant BCR-ABL mutants, except T315I gatekeeper mutation, which occurs in up to 20% of patients with resistant CML.256,257 Ponatinib is a third-generation Bcr-Abl1 inhibitor with activity against T315I mutation.258 The binding pattern of ponatinib is similar to imatinib, except that the carbon-carbon triple bond extending from the purine of ponatinib enforces compatibility with T315I residue.