Dickkopf1(DKK-1)基因甲基化在急性白血病中的表达分析  

Analysis of methylation of the Dickkopf1(DKK-1) gene in acute leukemia

作　　者：朱珣珣[1] 朱传升[2] 王焱[2] 徐文伟[2] 董琳[2] 郭燕[2] 李洪丽[1] 毕可红[2] 

机构地区：[1]山东大学医学院,济南250012 [2]山东大学附属千佛山医院血液科,济南250014

出　　处：《山东大学学报（医学版）》2012年第5期84-87,共4页Journal of Shandong University:Health Sciences

基　　金：山东省科技攻关项目(2006GG3202037)

摘　　要：目的探讨WNT/β-catenin通路的关键抑制因子Dickkopf1(DKK-1)基因异常甲基化与急性白血病(AL)发病机制的相关性。方法采用逆转录聚合酶链式反应(RT-PCR)方法检测4个AL细胞系(NB4、Jurkat、Molt-4、CEM)、65例AL患者及20例正常对照骨髓单个核细胞中DKK-1基因mRNA的表达情况;采用甲基化特异性PCR(M SP)方法检测各标本及细胞系中DKK-1基因启动子区域的甲基化状态。结果与正常对照组比较,AL患者DKK-1基因mRNA表达量显著降低(P<0.05);正常对照组标本单个核细胞中不存在DKK-1基因的甲基化;DKK-1在AL患者中甲基化率为37.7%(24/65),其中急性淋巴细胞白血病(ALL)患者中甲基化率为41.2%(14/34),急性髄系白血病(AML)患者中甲基化率为28.6%(10/31)。结论 DKK-1甲基化及异常表达在急性白血病中是一种较为普遍的现象,其参与了部分急性白血病的发病过程。Objective To investigate the relationship between the abnormal methylation of the Dickkopf1（DKK-1） gene,which is a key inhibiting factor of the WNT/β-catenin pathway,and acute leukemia（AL）.Methods Reverse Transcription Polymerase Chain Reaction（RT-PCR） was used to examine DKK-1 mRNA expression in 4 AL cell lines（NB4,Jurkat,Molt-4,and CEM） of 65 AL patients and 20 normal controls.Methylation-Specific Polymerase Chain Reaction（MSP） was used to examine the CpG-island methylation status of the DKK-1 gene in AL cell lines of AL patients and the controls.Results Compared with that in the normal controls,the expression of the DKK-1 gene was significantly reduced in the AL patients（P〈0.05）.None of the normal mononuclear cells showed methylation of the DKK-1 gene.DKK-1 methylation was found in 24 of the 65（37.7%） AL patients.The frequencies of aberrant DKK-1 methylation were 41.2%（14/34） in the acute lymphoblastic leukemia（ALL） patients,and 28.6%（10/31） in the acute myelocytic leukemia（AML） patients.Conclusions Methylation and aberrant expression of the DKK-1 gene are common in AL and also play a role in the pathogenesis of some AL.

关 键 词：基因 Dickkopf1 甲基化 白血病 

分 类 号：R733[医药卫生—肿瘤]