Distribution of cytogenetically and molecularly defined subsets of AML presenting in younger adults. Based on analysis of large cohorts of patients and patterns of mutual exclusivity between cytogenetic and molecular genetic features, the majority of AML cases can be segregated into a number of biologically and prognostically distinct subgroups. In approximately a third of cases, AML is characterized by the presence of balanced chromosomal rearrangements,⁴  which lead to the generation of chimeric oncoproteins, considered to be initiating events in disease pathogenesis. These chromosomal abnormalities are mutually exclusive of mutations in the nucleophosmin gene (NPM1) and biallelic CEBPA (biCEBPA) mutations, which are recognized as recurrent AML-defining genetic abnormalities and typically associated with a normal karyotype. Recent studies have established a close correlation between complex karyotype/monosomal karyotype and underlying mutation in the TP53 gene,⁵  which defines a biological subgroup with very poor prognosis. Recent studies have distinguished a mutational profile involving alterations to a panel of genes including those encoding ASXL1 and spliceosome components associated with secondary AML arising on a background of myelodysplasia (MDS).⁶  For each cytogenetically and genetically defined subset of AML denoted in the pie chart, frequent associated cooperating mutations are shown in the respective boxes. Mutational frequencies are derived from integration of data from previous studies.⁴