Nonrandom chromosomal abnormalities present at the time of diagnosis of acute myeloid leukemia (AML) are used to direct treatment decisions for patients as they are known predictors of response to therapy and disease-free and overall survival. During recent years, molecular analyses have revealed a number of acquired gene mutations and changes in gene and microRNA expression that allow for classification of patients into cytogenetic and molecular subsets with distinct clinical characteristics. Aside from outcome prediction and stratification to risk-adapted therapies, these discoveries have also provided insight into mechanisms of leukemogenesis and potential targets for therapeutic intervention. While the greatest improvement in risk stratification made by these advances has been in patients with cytogenetically normal (CN) AML, a group that comprises 40–50 % of all patients with newly diagnosed disease, recurrent mutations with prognostic significance have also played a key role in other cytogenetic groups (i.e., core binding factor AML and AML with complex karyotype). The importance of these molecular abnormalities has been recognized, and select mutations are now included in classification systems (i.e., World Health Organization and European LeukemiaNet) as a complement to cytogenetics. In this chapter, we review these recent genetic findings and discuss their prognostic significance and clinical implications.
