Understanding FLT3 Inhibitor Resistance to Rationalize Combinatorial AML Therapies

Summary: Patients treated with Fms-like tyrosine kinase 3 (FLT3) inhibitor–based acute myeloid leukemia therapies nearly always develop resistance. In this issue, Alotaibi and colleagues describe the patterns of mutations that emerge upon relapse after FLT3 inhibitor therapy after initial response, as well as in treatment-refractory disease in a single-institution study; the findings offer insights for sequential therapies targeting the dominant clone at the time of relapse.