Impact of genomics in the clinical management of patients with cytogenetically normal acute myeloid leukemia

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease. Cytogenetics and FISH have contributed to the stratification of AML patients into favorable, intermediate, and unfavorable risk categories. However, until recently, the prognostic stratification and treatment decision for the intermediate risk category, mostly comprising AML patients with normal cytogenetics (CN-AML), has been difficult due to the scarce knowledge of the molecular alterations underlying this large AML subgroup (which accounts for about 50% of all adult AML). During the past decade, the discovery of numerous mutations associated with CN-AML has resulted in significant advances in the AML field. Here, we review the biological characteristics of the most common mutations underlying CN-AML and outline their clinical impact in the following settings: (i) definition of new molecular leukemia entities in the WHO classification; (ii) risk stratification of CN-AML patients according to mutational profile; and (iii) monitoring of minimal residual disease by specific quantitative molecular assays.