Recurrent driver mutations in FMS-related receptor tyrosine kinase 3 (FLT3) occur in around one-third of patients with de novo acute myeloid leukemia (AML). Although most FLT3 mutations are secondary events in leukemogenesis, they are associated with accelerated clonal expansion and disease progression, and treatment with the tyrosine kinase inhibitor midostaurin has been shown to increase patients’ long-term survival. However, the efficacy of FLT3 inhibitors in eliminating FLT3-mutated clones is variable.