慢性粒细胞白血病骨髓细胞的SFRP2基因启动子高甲基化

目的 研究慢性粒细胞白血病(chronic myeloid leukemia,CML)骨髓细胞SFRP2基因启动子甲基化状态,探讨SFRP2基因启动子甲基化在CML发病机制中的作用.方法 分别采用RT-PCR、甲基化特异性PCR(methylation-specific PCR,MSP)方法检测CML细胞系K562细胞...

Hypermethylation in SFRP2 promoter in human leukemia K562 cells and bone marrow specimen with chronic myeloid leukemia

Objective To determine the methylation status of secreted frizzled-related protein 2(SFRP2) gene in chronic myeloid leukemia(CML) bone marrow cells,and try to find the role of its promoter methylation during the tumorigenesis of CML.Methods The expression of SFRP2 in CML cell line K562,bone marrow specimens of identified CML patients and health volunteers were detected with semi-quantitative PCR(RT-PCR).The methylation status of SFRP2 promoter was detected in K562 cells and CML bone marrow specimens by methylation-specific PCR(MSP).After K562 cells was treated with pharmacological demethylation 5-aza-2’deoxycytidine(Aza) and trichostatin A(TSA),the expression of SFRP2 was detected again with RT-PCR.Results SFRP2 was silenced in K562 cells,expressed in 22.0%(4/18) CML bone marrow specimens,and detected in all normal bone marrow samples(100.0%,8/8,P<0.05).The frequencies of SFRP2 promoter methylation were 100%,66%(25/38) and 0(0/13) respectively in K562 cells,CML bone marrow and normal bone marrow specimens(P<0.05).Pharmacological demethylation treatment dramatically induced mRNA expression of SFPR2,and this reactivation was associated with an increase of unmethylation alleles.Conclusion The promoter of SFRP2 gene are hypermethylated in CML,which be one of the molecular mechanisms of CML.Its hypermethylation might serve as a new biomarker for CML.