Mechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment

The presence of FLT3 mutations in acute myeloid leukemia (AML) carries a particularly poor prognosis, making the development of FLT3 inhibitors an imperative goal. The last decade has seen an abundance of clinical trials using these drugs alone or in combination with chemotherapy. This culminated with the recent approval by the US Food and Drug Administration of Midostaurin for the treatment of FLT3-mutated AML. Initial success has been followed by the emergence of clinical resistance. Although novel FLT3 inhibitors are being developed, studies into mechanisms of resistance raise hope of new strategies to prevent emergence of resistance and eliminate minimal residual disease.