Dual roles of EZH2 in acute myeloid leukemia

Abstract

The histone lysine N-methyltransferase EZH2 is the enzymatic component of the polycomb repressive complex 2 (PRC2) that controls stem cell maintenance and differentiation. Mutations in EZH2 exert context-specific and sometimes opposing effects on tumorigenesis. Oncogenic gain-of-function mutations found in patients with lymphoid malignancies (Morin et al., 2010) led to developing small molecule inhibitors of EZH2 that are currently being tested in clinical trials. Also, overexpression of the non-mutated EZH2 in breast, prostate, and renal cancers was associated with unfavorable prognosis (Kim and Roberts, 2016). In contrast, loss-of-function mutations in EZH2 were found in myeloproliferative neoplasms (MPNs; Ernst et al., 2010), and loss of Ezh2 accelerated progression in mouse models of MPN, indicating that in this context, EZH2 functions as a tumor suppressor (Sashida et al., 2016; Shimizu et al., 2016).