DOT1L is the only known methyltransferase that catalyzes mono-, di- and tri-methylation of lysine 79 on histone H3 (H3K79me1/2/3) and has been identified as a critical component of oncogenic “Mixed Lineage Leukemia 1” (MLL1/KMT2A) complexes in KMT2A-rearranged and NPM1c mutant acute leukemia [20–23]. This evidence concerns the gene DOT1L and acute leukemia.