In AML, recent detailed mechanistic studies have identified DOT1L as a vulnerability of MLL-rearranged leukemia (Bernt et al., 2011), and both a mechanistic and an RNAi-based epigenetics-focused screen identified BRD4 as a therapeutic target against AMLs of different genotypes (Dawson et al., 2011, Zuber et al., 2011). Here, KMT2A is linked to acute myeloid leukemia.