Molecular genetics of acute myeloid leukemia: clinical implications and opportunities for integrating genomics into clinical practice

Advances in sequencing technologies have led to the discovery of a series of mutations in a sizeable proportion of patients with acute myeloid leukemia (AML) over the last 10 years. Clinical correlative studies are now beginning to decipher the clinical importance, prevalence and potential prognostic significance of these mutations in AML but few studies have assessed the clinical implications of these mutations in a comprehensive fashion. Nonetheless, mutations in DNMT3A, TET2, and ASXL1 are emerging as important adverse prognosticators in subsets of patients with AML independent of FLT3 mutations whereas mutations in IDH2 at residue 140 are potential predictors of improved outcome in AML. Further improvements in cost, throughput, and clinical validation of second-generation sequencing technologies may allow for clinical implementation of comprehensive genetic profiling in the clinical care of AML patients.