恶性血液病细胞系分泌型卷曲相关蛋白基因启动子CpG岛甲基化状态的检测及意义  

Methylation Status of CpG Islands in Secreted Frizzled-related Protein Gene Promoter Region of Malignant Hematopoietic Cell Lines

作　　者：徐成波[1] 沈建箴[1] 沈松菲[1] 傅海英[1] 吴雪梅[1] 吴淡森[1] 朱艺芳[1] 陈璐[1] 

机构地区：[1]福建医科大学附属协和医院血液科,福建省血液病研究所,福建福州350001

出　　处：《中国实验血液学杂志》2009年第6期1487-1491,共5页Journal of Experimental Hematology

基　　金：福建省自然科学基金资助项目(编号CO540014);福建省百千万人才工程基金资助项目(编号303052801);福建医科大学教授基金资助项目(编号JS06080)

摘　　要：为了研究分泌型卷曲相关蛋白(secreted frizzled-related protein,SFRP)家族基因启动子CpG岛的甲基化状态,探讨SFRP基因启动子区CpG岛的异常甲基化状态与恶性血液病发病机制的可能联系,采用甲基化特异性PCR(Methylation-specific PCR,MSP)的方法检测了9种恶性血液病细胞系及正常人外周血单个核细胞中SFRP基因启动子区的甲基化状态。结果显示:9种恶性血液病细胞系中SFRP1、2基因启动子区均呈高甲基化状态,CA46、HL60和U937细胞中的SFRP4基因以及U266细胞中的SFRP5基因启动子区呈部分甲基化状态,其他细胞系SFRP4、5基因启动子均呈完全甲基化状态。正常人外周血单个核细胞中SFRP1、2、4、5基因启动子区均呈非甲基化状态。结论:SFRP基因启动子区异常甲基化模式与恶性血液病的发生密切相关。SFRP基因启动子区的甲基化状态有可能成为恶性血液病新的分子诊断标记物。To investigate the methylation status of CpG islands of the secreted frizzled-related protein（SFRP） gene promoter region in malignant hematopoietic cell lines, and to explore the possible relationship of CpG abnormal methylation status with pathogenic mechanism of hematologic malignancies. Methylation-specific PCR was used to detect the status of SFRP gene promoter region in nine malignant hematopoietic cell lines and peripheral blood mononuclear cells from healthy people. The results indicated that hypermethylations of 2 genes coding for SFRP1 and 2 were present in nine malignant hematopoietic cell lines, however, methylation and unmethylation of SFRP4 were both detected in CA46, HL60 and U937 cell lines, and SFRP5 in U266 as well. None of the normal mononuclear ceils showed methylation of SFRP 1 - 5 genes. It is concluded that the hypermethylation of SFRP genes is related to the evolution of malignant hematopoiesis. Methylation of SFRP genes may serve as potential independent biomarkers for early detection of hematologic malignancies.

关 键 词：恶性血液病 分泌型卷曲相关蛋白 CPG岛 甲基化 

分 类 号：R733[医药卫生—肿瘤]