Because R/R AML is demonstrably polyclonal in nature, FLT3 TKIs may elicit clonal pressure to select for drug-resistant tumor cell populations with additional mutations that promote leukemic growth independent of the activation state of the FLT3 kinase [11–13], as well as for clones that lack FLT3 mutations entirely [11, 12]. This evidence concerns the gene FLT3 and acute myeloid leukemia.