Although the outcome of these gain-of-function mutations has documented a role of EZH2 as an oncogenic mediator, other findings suggest that EZH2 might function as a tumor suppressor because EZH2 loss-of-function is associated with development of malignancySpecifically, EZH2 inactivating deletion, frameshift, nonsense and missense mutations have been identified in myelodysplastic syndromes (MDS), myeloproliferative neo­plasms (MPN) and MDS-MPN overlap disorders [27, 28]. This evidence concerns the gene EZH2 and myeloproliferative disorder.