Examples of integrated genetic and epigenetic analysis of human AML leading to potential epigenetic treatment. The integrated analysis of gene mutations, DNA methylation, and histone modifications (A) has revealed multiple AML subtypes with specific mutations in association with specific epigenetic alterations. Four examples are indicated (B). Mutations in IDH1/2 and TET2 result in aberrant patterns of DNA cytosine methylation and hydroxymethylation (C), whereas rearrangements affecting the EVI and MLL loci result in alterations of chromatin marks (C). For each of these 4 examples, certain epigenetic inhibitors have been designed or are predicted to be active, offering the potential to translate these findings to clinical trials in human patients (D). The various inhibitors are discussed in more detail in the text.