CHD5基因启动子甲基化调控p19Arf/p53/p21Cip1信号通路促进急性髓系白血病发病的研究  

Methylation of CHD5 Gene Promoter Regulates p19Arf/p53/p21Cip1 Pathway to Facilitate Pathogenesis of Acute Myeloid Leukemia

作　　者：吴明彩[1,2] 蒋明 董婷 吕俊 方基勇[1] 徐蕾 韦中玲[5] 章尧[1,2] WU Ming-Cai;JIANG Ming;DONG Ting;LV Jun;FANG Ji-Yong;XU Lei;WEI Zhong-Ling;ZHANG Yao(Department of Biochemistry of Wannan Medical College,Wuhu 241002,Anhui Province,China;Anhui Province Key Laboratory of Active Biological Macromolecules,Wuhu 241002,Anhui Province,China;Wuhu Second Sanatorium for Retired Cadres,Anhui Military Area,Wuhu 241001,Anhui Province,China;Encephalopathy Center,The First Affiliated Hospital of the University of Traditional Chinese Medicine in Anhui,Hefei 230031,Anhui Province,China;Department of Hematology,Yijishan Hospital,Wannan Medical College,Wuhu 241001,Anhui Province,China)

机构地区：[1]皖南医学院生物化学教研室,安徽芜湖241002 [2]安徽省活性大分子重点实验室,安徽芜湖241002 [3]安徽省军区芜湖市第二离职干部休养所,安徽芜湖241002 [4]安徽中医药大学附属第一医院脑病中心,安徽合肥230031 [5]皖南医学院弋矶山医院血液内科,安徽芜湖241001

出　　处：《中国实验血液学杂志》2019年第4期1001-1007,共7页Journal of Experimental Hematology

基　　金：安徽高校自然科学研究项目重点项目(KJ2018A0262,KJ2016A731);安徽省自然科学基金项目(1808085MH263);皖南医学院校重点科研项目培育基金(WK2014Z01);皖南医学院博士启动基金(WYRCQD201801)

摘　　要：目的:探讨急性髓系白血病患者(AML)骨髓中CHD5基因甲基启动子甲基化状态及其调控p19Arf/p53/p21Cip1信号通路促进AML发病的机制。方法:采用MSP检测AML组及对照组CHD5基因甲基化状态,应用实时定量RT-PCR和Westernblot检测CHD5、p19Arf、p53及p21Cip1的表达水平。结果:AML患者骨髓中CHD5基因甲基化率(39.06%)较对照组(6.67%)明显增高(P<0.05);CHD5基因甲基化与AML不同染色体核型相关(P=0.009),但与性别、年龄及临床分型无显著相关(P>0.05);AML患者CHD5相对表达水平明显低于对照组(P<0.05);存在CHD5甲基化AML患者p19Arf、p53及p21Cip1基因和蛋白表达水平较对照组降低。结论:AML患者CHD5基因启动子的高甲基化可导致CHD5、p19Arf、p53和p21Cip1表达水平下降,从而可能通过调控p19Arf/p53/p21Cip1途径减弱对白血病细胞增殖抑制作用,促进AML的发生。Objective:To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients,and the underlying mechanism for initiating the pathogenesis of AML via p19Arf/p53/ p21Cip1 pathway.Methods:Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients,and the iron-deficiency anemia (IDA) samples were served as control.The expression of CHD5,p19Arf,p53 and p21Cip1 was determined by real-time quantitative reverse transcriptase PCR and Western blot.Results:The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%).The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P < 0.01),but did not correlate with the patient′s sex,age and clinical classification (P > 0.05).The mRNA expression of CHD5 gene in AML decreased,compared with control group,the mRNA and protein expression of p19Arf,p53 and p21Cip1 in AML with CHD5 methylation promoter decreased. Conclusion:The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5,p19Arf, p53 and p21Cip1 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19Arf,p53 and p21Cip1 pathway,thus promotes the occurence of AML.

关 键 词：急性髓系白血病 CHD5基因 启动子 DNA甲基化 p19Arf P53 p21Cip1 

分 类 号：R733.71[医药卫生—肿瘤]