Molecular targeted therapy in acute myeloid leukemia

The treatment of acute myeloid leukemia has not changed significantly over the last 40 years. Recent progress in understanding the biology of this disease and identification of driver mutations has ushered in a new era of molecular therapeutics. Although a number of molecular markers and pathways have been identified and may serve as potential therapeutic targets, the best studied amongst these include FMS like tyrosine kinase 3 (FLT3), RAS/RAF/MEK/ERK and Janus kinase (JAK-2). In this review we discuss the molecular biology of AML, with a special focus on the above mentioned pathways. We discuss novel molecular targeted therapies that are in preclinical and clinical development. These include AC-220, sorafenib and midostaurin in FLT3 mutated patients; GSK1120212 and MSC1936369B in RAS mutated patients; and INCB018424 in JAK2 mutated patients. Identification of such molecular mutations and appropriate use of targeted therapies, either alone or in combinations, may eventually revolutionize the treatment of AML.