Targeted therapies in the treatment of adult acute myeloid leukemias: current status and future perspectives.

The rapid advancement of next-generation sequencing techniques and the identification of molecular driver events responsible for leukemia development are opening the door to new pharmacologic-targeted agents to tailor treatment of acute myeloid leukemia (AML) in individual patients. However, the use of targeted therapies in AML has met with only modest success. Molecular studies have identified AML subsets characterized by driver mutational events, such as NPM1, FLT3-ITD and IDH1-2 mutations, and have provided preclinical evidence that the targeting of these mutant molecules could represent a valuable therapeutic strategy. Recent studies have provided the first pieces of evidence that FLT3 targeting in FLT3-mutant AMLs, IDH1/2 inhibition in IDH-mutant AMLs and targeting membrane molecules preferentially expressed on leukemic progenitor/stem cells, such as CD33 and CD123, represent a clinically valuable strategy.