Recurrent genomic alterations in epigenetic writer, reader, and eraser proteins, such as DNA methyltransferase 3A (DNMT3A), TET1/2, IDH1/IDH2, EZH2, mixed-lineage leukemia (MLL), NSD1/3, AF10, ENL, and other epigenetic regulators have been cataloged in AML, inspiring a wave of preclinical studies aimed at uncovering causal links between epigenome dysregulation and leukemogenesis (see Figure 1 and Table 1). Here, KMT2A is linked to acute myeloid leukemia.