Molecularly targeted therapy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is molecularly heterogeneous. Formerly categorized cytogenetically and molecularly, AML may be classified by genomic and epigenomic analyses. These genetic lesions provide therapeutic targets. Genes targeted currently include mutated FLT3, NPM1 and KIT with drugs entering Phase III trials. Complete remission can be achieved in relapsed/refractory AML, albeit mostly transient. Mutated epigenetic modifiers, including DNMT3A, IDH1/2 and TET2, can be targeted by small molecule inhibitors, hypomethylating agents and histone deacetylase inhibitors. Other agents include cellular signaling pathway inhibitors and monoclonal antibodies against myeloid-associated antigens. Combinatorial strategies appear logical, mostly involving smaller molecular inhibitors partnering with hypomethylating agents. Currently limited to relapsed/refractory AML, targeted therapies are increasingly tested in frontline treatment with or without standard chemotherapy.