EZH2, via its catalysis of lysine 27 on histone H3 (H3K27me3), plays a vital role in gene expression, and EZH2 overexpression is traditionally associated with cancer progression; interestingly and uniquely, AML induced by EZH2 alteration is thought to be related to loss of function in the context of EZH2 as a tumor suppressor, whereas EZH2 may demonstrate oncogenicity in the maintenance setting [137,138]. This evidence concerns the gene EZH2 and acute myeloid leukemia.