急性白血病组蛋白乙酰化修饰及其对错配修复基因表达的调控作用  

Modification of histone acetylation and its regulation effect to the expression of mismatch repair genes in acute leukemia

作　　者：王彩霞[1] 毛平[1] 杜庆华[1] 王顺清[1] 李庆山[1] 张玉平[1] 应逸[1] 莫文健[1] 周志衡[2] 

机构地区：[1]广州医学院附属广州市第一人民医院血液科,510100 [2]广州医学院公共卫生与全科医学学院

出　　处：《白血病．淋巴瘤》2011年第3期132-136,共5页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金（30471644）;广东省自然科学基金（06112013）;广州市科技局项目（2008A1-E4011-8）

摘　　要：目的探讨急性白血病患者组蛋白乙酰化修饰规律，并探索组蛋白乙酰化对错配修复基因hMSH2和hMLH1差异表达的调控作用。方法用反转录-聚合酶链反应（RT．PCR）方法检测56例急性白血病患者和30名健康志愿者单个核细胞（MNC）的错配修复基因hMSH2和hMLH1mRNA的表达，用Western blot法检测组蛋白H3、H4、去乙酰化酶（HDAC1）、hMSH2和hMLH1基因的蛋白表达情况。用组蛋白去乙酰转移酶抑制剂（TSA）诱导30例白血病患者MNC乙酰化，并检测处理后MNC的组蛋白H3、H4、HDAC1、hMSH2和hMLH1的表达状态变化。结果急性白血病组的hMSH2和hMLH1、组蛋白H3、H4的蛋白表达量分别为0．4610±0．1211、0．4013±0．1143、0．4103±0．1241和0．4251±0．1081，均明显低于健康志愿者组的蛋白表达量（0．9461±0．1841、0．9960±0．2021、0．8971±0．1194、0．9513±0．1953），差异均有统计学意义（t值分别为3．341、3．935、2．843、3．575，P〈0．05）；而急性白血病患者组的HDAC1表达（0．8841±0．2018）高于健康志愿者组的表达量（0．5142±0．1340），差异有统计学意义（t=2．634，P〈0．05）；TSA作用于白血病单个核细胞后，组蛋白H3、H4、hMSH2和hMLH1的表达上调，分别比阴性对照组表达上调2．9倍、3．4倍、1．5倍和1．6倍，而HDAC1的蛋白表达出现明显的抑制，表达下调为阴性对照组的40％。结论急性白血病患者的组蛋白乙酰化呈低表达现象，组蛋白乙酰化在急性白血病患者中对错配修复基因差异表达具有调控作用。Objective To explore the status of histone acetylation modification and their regulatory effect to hMSH2 gene and hMLH1 gene expression in acute leukemia. Methods Reverse transcription- polymerase chain reaction （RT-PCR） was used to measure the expression of hMSH2 and hMLH 1 mRNA, and Western blot was used to measure the expression of histone H3, H4, HDAC1, hMSH2 and hMLHI protein in mononuclear cells of 56 acute leukemia patients and 30 healthy volunteers. The mononuclear cells of 30 acute leukemia patients were treated with histone deacetylase inhibitors trichostatin A （TSA）, and measured the expression difference of histone H3, H4, HDAC1, hMSH2 and hMLH1 in the mononuclear cells treated with TSA. Results The protein expression levels of hMSH2, hMLH1, histone H3 and histone H4 in those mononuclear cells of acute leukemia patients were 0.4610±0.1211, 0.4013±0.1143, 0.4103±0.1241 and 0.4251±0.1081, respectively, which were significantly decreased comparing with those of healthy volunteers （0.9461±0.1841, 0.996±0.2021, 0.8971±0.1194 and 0.9513±0.1953） （t = 3.341, 3.935, 2.843 and 3.575, respectinely, P 〈0.05）. The protein expression levels of HDAC1 （0.8841±0.2018） of acute leukemia patients was significantly increased comparing with those of healthy volunteers （0.5142±0.1340） （t = 2.634, P 〈0.05）. After treatment with TSA for 48 hours, the protein expression of hMSH2 was increased nearly 1.5-fold, hMLH1 about 1.6-fold, H3 about 2.9-fold and H4 about 3.4-fold comparing with the negative control groups （P 〈0.05）, while the protein expression of HDAC1 were decreased comparing with the negative control groups by 40 %. Conclusion There was an low expression phenomenon of historic acetylation in acute leukemia, and histone acetylation played an important role in regulation of the mismatch repair gene expression in acute leukemia.

关 键 词：白血病 急性 组蛋白乙酰化 错配修复基因 

分 类 号：R733.71[医药卫生—肿瘤]