Hypermethylation of GSTM5 and its effect on oxidation in myelodysplastic syndrome  

作　　者：Chi Wang Yafei Yu Qing Chang Tengteng Dong Liye Wang Mianyang Li 

机构地区：[1]Department of Clinical Laboratory Medicine,The First Medical Center,Chinese PLA General Hospital,Beijing,China

出　　处：《iLABMED》2024年第2期108-124,共17页智能检验医学（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Number:61971443。

摘　　要：Background:Hypermethylation of glutathione-S-transferase 5(GSTM5)and its effect on oxidation in the pathogenesis of myelodysplastic syndrome(MDS)were investigated.Methods:GSTM5 methylation was detected in bone marrow(BM)samples from MDS patients,acute myeloid leukemia(AML)patients,and control in-dividuals using methylation-specific PCR and MassARRAY analysis.Bisulfite sequencing PCR was performed to verify methylation levels,while mRNA levels were determined using reverse transcription polymerase chain reaction.Correlations between GSTM5 methylation and clinical parameters were analyzed.The MDS cell line,SKM-1,was treated with decitabine,buthionine sulfoximine,or overexpression of GSTM5,and the glutathione level and cell viability were detected.Results:The MassARRAY analysis revealed significant differences in GSTM5 methylation levels between the MDS and control groups.GSTM5 methylation levels were significantly increased in the high-risk subgroup and showed a significant association with MDS progression to AML(hazard ratio=3.6).Levels of GSTM5 mRNA were significantly decreased in the MDS group,exhibiting a negative correlation with the GSTM5 gene methylation level.Normal BM HS-5 cells exhibited significantly lower levels of GSTM5 methylation than SKM-1 cells.Overexpression of GSTM5 in SKM-1 cells or treatment with buthionine sulfoximine or decitabine resul-ted in inhibition of proliferation and significantly decreased glutathione levels.Conclusions:GSTM5 plays an anti-oxidative role in MDS and the tumor suppressor effect of GSTM5 may be mediated by reducing glutathione levels.GSTM5 hypermethylation and low levels of GSTM5 expression may be prog-nostic markers for MDS.

关 键 词：GLUTATHIONE GSTM5 METHYLATION myelodysplastic syndrome PROGNOSIS 

分 类 号：R446[医药卫生—诊断学]