Previous epigenetics research in myelodysplastic syndromes (MDS) mainly focused 
on the DNA methylation of tumor suppressor genes. Recent studies reported that 
around 6% of MDS patients have several EZH2 mutations including missense, 
frameshift and truncated mutations. Histone methyltransferase EZH2 plays a 
critical role in epigenetic regulation as a bridge between histone 
methylation/deacetylation and DNA methylation. EZH2 is frequently overexpressed 
and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as 
a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with 
poor survival. Many questions still need further discussion. Moreover, 
3-deazaneplanocin can reduce EZH2 levels and H3K27 trimethylation, and 
synergistic effects are seen in combination with DNA demethylation agents or 
histone deacetylation inhibitors. All of the above give us more chances to 
improve epigenetic therapy in MDS. Therefore, the molecular mechanisms of EZH2 
in tumorigenesis and the role of EZH2 in MDS are studied.