错配修复基因hMSH2与慢性粒细胞白血病相关性研究  

Study on the Relationship of Mismatch Repair Gene hMSH2 and Chronic Myeloid Leukemia

作　　者：王志刚[1,2,3] 吕小林[4] 戴革[1,2,3] 袁利亚[1,2,3] 赵林[1,2,3] 胡银英[1,2,3] 黄艳琴[1,2,3] 袁铿[1,2,3] 

机构地区：[1]江西省医学科学研究院,江西南昌330006 [2]江西省医学免疫和免疫治疗重点实验室,江西南昌330006 [3]南昌大学免疫与免疫治疗研究所,江西南昌330006 [4]南昌大学第一附属医院,江西南昌330006

出　　处：《现代生物医学进展》2015年第12期2225-2229,共5页Progress in Modern Biomedicine

基　　金：江西省自然基金项目(20114BAB205021)

摘　　要：目的:通过对慢性粒细胞白血病(chronic myeloid leukemia,CML)患者骨髓细胞中错配修复基因(mismatch repair,MMR)h MSH2的表达水平及其调控机制的分析,探讨h MSH2与慢性粒细胞白血病疾病进展的联系。方法:用实时定量PCR方法检测10例对照,27例CML患者(包括慢性期9例,进展期8例,急变期10例)骨髓中4个MMR基因(h MSH2、h MSH6、h MLHl、h PMS2)m RNA的表达;用MSP方法检测MMR基因启动子区甲基化水平;用Western blot方法观察MMR蛋白水平在各组之间的差异。结果:与正常对照比较,CML患者的h MSH2的表达明显降低(P<0.05),其表达随疾病恶化而下降,依次为急变期<加速期<慢性期,而h MLHl、h PMS2、h MSH6的表达却未见异常;27例CML患者中出现3例h MSH2启动子区高甲基化。结论:CML患者的h MSH2表达水平比正常人显著降低,且随着疾病恶化其表达水平逐下降,提示h MSH2可能与CML疾病进展相关。Objective： To investigate the expression and regulation mechanism of mismatch repair （MMR） gene hMSh2 of bone marrow in chronic myeloid leukemia （CML）, and study the relationship of mismatch repair gene hMSH2 and chronic myeloid leukemia progression. Methods： Expression of MMR genes hMSH2, hMSH6, hMLH1 and hPMS2 mRNAs in 27 CML patients （including chronic phase 9, accelerated phase 8 and blast crisis 10 cases） and the normal control group （10 cases） were detected by quantitative polymerase chain reaction （Q-PCR）; methyl-specific PCR （MSP） was used to analyze methylation status ofhMLH1 and hMSH2 promoters in CML; the expression of hMSH2 protein was detected by Western blot. Results： The expression of hMSH2 was significantly lower in CML than in normal control （P 〈0.05）, and decreased gradually with the deterioration of disease（blast crisis〈accelerated phase〈chronic phase）, but there was no statistical significance in the expression of hMSH6, hMLH1 and hPMS2 between CML and the control groups. In addition, hMSH2 promoter hypermethylation existed in 3 of 27 CML patients. Conclusion： Expression Qf hMSH2 was significantly lower in CML than in the control group and showed a gradual decline according to CML progress, which indicated that hMSH2 might be correlated with CML progress.

关 键 词：慢性粒细胞白血病 错配修复基因 HMSH2 

分 类 号：R733.72[医药卫生—肿瘤]