Overexpression of the EZH2, RING1 and BMI1 genes is common in myelodysplastic syndromes: relation to adverse epigenetic alteration and poor prognostic scoring.
Epigenetics refers to the study of clonally inherited changes in gene expression without accompanying genetic changes. Previous research on the epigenetics of myelodysplastic syndromes (MDS) mainly focused on the inactivation of tumor suppressor genes as a result of DNA methylation. However, the basic molecular pathogenesis of epigenetics in MDS remains poorly understood. Recent studies have revealed that DNA methylation and histone modification may be controlled by Polycomb-group (PcG) proteins, which may give new clues toward understanding the epigenetic mechanism of MDS. In this study, we explored for the first time the expression of PcG genes, including EZH2, EED, SUZ12, RING1, and BMI1, in various MDS subsets and acute myeloid leukemia (AML), as well as the relationship between the expression of PcG genes and epigenetic alteration and prognosis-risk scoring. Patients with MDS/AML showed overexpression of EZH2, RING1, and BMI1 genes compared to their expression levels in patients with non-clonal cytopenia diseases. The MDS patients with DNA methylation had higher EZH2 expression than those without DNA methylation. The patients who received decitabine treatment presented significantly reduced expression of EZH2 and RING1 besides decreased p15(INK4B) methylation after decitabine treatment. Moreover, overexpression of EZH2, RING1, and BMI1 was always linked to poor prognostic scoring. In conclusion, overexpression of the EZH2, RING1, and BMI1 genes is common in MDS and indicate poor prognosis. The products of these genes might participate in epigenetic regulation of MDS. These studies may also contribute to our understanding of the effective mechanism of decitabine.
Department of Hematology, The Sixth people Hospital, Shanghai JiaoTong University, ShangHai Jiaotong University School of Medicine, Shanghai, 200233, People's Republic of China.
Feng
F
Xu
Xiao
X
Li
Lingyun
L
Wu
Qingxia
Q
Zhang
Rui
R
Yang
Yujuan
Y
Yang
Zheng
Z
Zhang
Qi
Q
He
Chunkang
C
Chang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012107:Research Design; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human