The role of histone methyltransferase EZH2 in myelodysplastic syndromes

Department of Hematology, the Sixth People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China.
Expert Review of Hematology (Impact Factor: 2.07). 04/2012; 5(2):177-85. DOI: 10.1586/ehm.12.5
Source: PubMed


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.

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    • "EZH2 is located on chromosome 7q, and loss of this chromosome in MDS has long been recognized as a poor prognostic indicator [76] [77]. Further research has found that it is likely that this poor prognosis in these patients is associated with loss of EZH2 [75] [78] [79]. "
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