The Future of Targeting FLT3 Activation in AML

Abstract

Internal tandem duplications (ITD) and tyrosine-kinase domain (TKD) mutations of the FMS-like tyrosine-kinase 3 (FLT3) can be found in up to one third of patients with acute myeloid leukemia (AML) and confer a poor prognosis. First discovered 20 years ago, these mutations were identified as viable therapeutic targets, and FLT3 tyrosine-kinase inhibitors (TKIs) have been in development for the last decade with steadily increasing potency. However, FLT3-mutated AML often acquires resistance to the growing armamentarium of FLT3 inhibitors through a variety of mechanisms. In this review, we discuss the distinct clinical phenotype of FLT3-mutated AML, historically and currently available therapeutics, mechanisms of resistance, ongoing trials, and future outlook at treatment strategies.

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