EB病毒和人巨细胞病毒感染对儿童急性淋巴细胞白血病PTEN及hTERT基因甲基化的影响  

Effects of Epstein- Barr virus and cytomegalovirus infection on childhood acute lymphoblastic leukemia gene methylation

作　　者：祁新坤[1] 舒逸[1] 秦茹[1] 邹琳[1] 

机构地区：[1]重庆医科大学附属儿童医院临床分子医学中心//儿童发育疾病研究省部共建教育部重点实验室//儿科学重庆市重点实验室//重庆市干细胞治疗工程技术研究中心,重庆400014

出　　处：《南方医科大学学报》2013年第11期1678-1681,共4页Journal of Southern Medical University

基　　金：重庆市杰出青年基金(2010BA5008)

摘　　要：目的探讨EB病毒(EBV)与人巨细胞病毒(HCMV)感染对儿童急性淋巴细胞白血病(ALL)相关基因PTEN及hTERT甲基化的影响及其意义。方法收集初发儿童ALL患者外周血标本100例,取血浆进行病毒感染血清学检测,据血清学结果分为EBV单独感染组(20例),HCMV单独感染组(14例)EBV、HCMV联合感染组(41例)及全阴性对照组(15例)。从外周血标本分离单个核细胞,提取DNA,亚硫酸氢钠盐修饰后,采用甲基化特异性(MS)-PCR法检测各组PTEN及hTERT基因DNA启动子区甲基化水平的变化。结果 EBV、HCMV联合感染组与对照组及单独感染组相比PTEN基因甲基化水平明显降低(P<0.05),hTERT甲基化水平有明显升高(P<0.05)。结论在儿童急性淋巴细胞白血病中,EBV和HCMV病毒联合感染使肿瘤相关基因PTEN及hTERT的甲基化水平改变,提示病毒感染可参与到基因表观遗传学调控,后续的研究还需进一步证明。Objective To investigate the associations between Epstein-Barr virus （EBV） and human cytomegalovirus （HCMV） infections and the methylation levels of PTEN and hTERT genes and explore their roles in children with acute lymphoblastic leukemia （ALL）. Methods Blood samples from 100 children with newly diagnosed acute lymphoblastic leukemia were centrifuged for serological detection of EBV and HCMV, and the patients were divided accordingly into EBV-infected group （n=20）, HCMV-infected group （n=14）, EBV and HCMV co-infected group （n---41）, and non-infected group （control group, n=15）. DNA was extracted from peripheral blood mononudear cells （PBMCs） and modified with bisulfite ammonia sodium. The methylation levels of the promoters of PTEN and hTERT genes were detected with methylation-specific polymerase chain reaction （MS-PCR）. Results Compared with those in non-infected group and EBV- or HCMV-infected group, the methylation levels of PTEN gene in the co-infected group were significantly decreased （i~〈0.05） while the methylation levels of hTERT gene significantly increased （P〈0.05）. Conclusion In children with acute lymphoblastic leukemia, EBV and HCMV co-infection cause changes in the methylation levels of PTEN and hTERT. These results may be associated with epigenetic changes caused by viral infections, and further studies are needed to further verify this hypothesis.

关 键 词：EB病毒 人巨细胞病毒 甲基化 急性淋巴细胞白血病 

分 类 号：R733.71[医药卫生—肿瘤]