ABO基因启动子CpG岛甲基化与白血病的相关性  

Correlation between DNA Methylation of the ABO Gene Promoter CpG Island and Leukemia

作　　者：徐华[1] 鲍国强[1] 王宝燕[2] 邢荷香[3] 叶世辉[3] 张建耕[3] 郁成雨[1] 檀英霞[1] 章扬培[1] 

机构地区：[1]军事医学科学院野战输血研究所血液生化和分子生物学研究室,北京100850 [2]西安交通大学医学院第一附属医院输血科,陕西西安710061 [3]陕西省血液中心,陕西西安710061

出　　处：《中国实验血液学杂志》2008年第2期240-246,共7页Journal of Experimental Hematology

摘　　要：近年来研究发现ABO血型与许多疾病的发生发展相关,某些肿瘤导致A、B血型物质减少的现象已日益引起关注。本研究探讨ABO基因启动子CpG岛甲基化与白血病的相关性。采用流式细胞仪和激光共聚焦显微镜检测了不同血型的健康人群和各种血液病患者外周血红细胞表面ABH抗原的相对含量,用PCR和MSP-PCR分别检测血液病患者和健康人ABO基因启动子DNA序列和CpG岛甲基化,以及ABO基因启动子-102位点的甲基化。结果发现,白血病患者均出现不同程度的A、B抗原减少;通过对比检测健康人和患者的ABO基因启动子序列,未发现有序列的不同,说明启动子序列高度保守;利用重亚硫酸盐对DNA样本进行修饰后,通过对健康人和患者的ABO基因启动子序列进行扩增和测序,发现健康人和再生障碍性贫血患者在ABO基因启动子的CpG岛区没有甲基化的位点,而急性髓性白血病(AML)、急性淋巴细胞白血病(ALL)、慢性粒细胞白血病(CML)和部分骨髓增生异常综合征(MDS)患者在位置为-102、-101、-100、-99和-97位置的C碱基均有甲基化的现象。结论:甲基化是造成白血病患者AB抗原下降的原因;-102、-101、-100、-99和-97这几个甲基化位点有可能是白血病的特异性表现;针对-102位点检测结果提示-102位点是否甲基化有可能作为白血病鉴别诊断中一个有意义的分子标识物。Recent studies have found that ABO blood group antigen is also closely related to the onset and develop- ment of many diseases. More and more attention is being paid to the decrease of A/B blood group antigen caused by some tumors. This study was purposed to investigate the correlation between DNA methylation of the ABO gene promoter CpG island and leukemia. The relative contents of ABH antigen on the surface of RBC from kinds of blood disease patients and healthy individuals were detected by using flow cytometey and confocal laser scanning microscopy. The DNA sequences and CpG methylation of ABO gene promoter in patients with hematopathy and healthy individuals, as well as the -102 site methylation of ABO gene promoter in patients with hematopathy and healthy individuals were detected by PCR and MSP-PCR respectively. The results showed that RBC from leukemia patients displayed different degree of A/B antigen decrease. The sequences of ABO gene promotor of patients with hematopathy were not different from healthy individuals indicating high conservation of promoter sequences. Comparision of sequences between patients with hematopathy and healthy individual indicated that CpG islands on ABO gene promoter either from blood disease patients or from healthy individual had no methylated site in AA patients, hut C residues at position -102, -101, -100, -99 and -97 on the promoter of ABO gene in AML, CML, ALL and some MDS patients were methylated. It is concluded that methylation of CpG islands in promoter of ABO gene may result in AB antigen decrease in patients with leukemia. The methylation sites -102, -101, -100, -99 and -97 may be specific for leukemia. The methylation of site -102 can be used as a molecular marker in differential diagnosis for leukemias.

关 键 词：白血病 ABO基因 CPG岛 基因甲基化 分子标识物 

分 类 号：R733.7[医药卫生—肿瘤] R457.11[医药卫生—临床医学]