慢性髓系白血病PDLIM4基因表达与其启动子甲基化水平的关系  

Expression pattern and promoter hypermethylation of PDLIM4 gene in patients with chronic myeloid leukemia

作　　者：李云[1] 钱军[1] 陈芹[2] 姚冬明[1] 王翠竹[1] 柴海彦[1] 杨静[1] 林江[2] 马吉春[2] 陈星星[1] 马玉娟[1] 

机构地区：[1]江苏大学附属人民医院血液科,江苏镇江212002 [2]江苏大学附属人民医院中心实验室,江苏镇江212002

出　　处：《江苏大学学报（医学版）》2013年第1期17-21,25,共6页Journal of Jiangsu University：Medicine Edition

基　　金：江苏省"333工程"资助项目(BRA2011085);国家自然科学基金资助项目(81270630);江苏省自然科学基金资助项目(BK2009206);2011年镇江市医学重点人才项目;镇江市社会发展资助项目(SH2010015;SH2011056);江苏省科技厅临床医学科技专项基金资助项目(BL2012056)

摘　　要：目的:分析慢性髓系白血病(chronic myeloid leukemia,CML)患者PDLIM4(PDZ and LIM domain 4)基因转录本表达状况、启动子高甲基化改变及临床相关性。方法:应用实时定量PCR(RQ-PCR)及实时定量甲基化特异性PCR(RQ-MSP)技术分别检测CML患者PDLIM4基因转录本及启动子甲基化水平。结果:8/36例(22%)CML患者存在PDLIM4低表达,低表达率与21例对照组间差异有统计学意义(P=0.021);PDLIM4表达水平和CML患者bcr/abl融合基因转录本正相关(r=0.434,P=0.043)。13/59例(22%)CML患者出现PDLIM4启动子高甲基化改变,而24例对照未显示高甲基化,两组差异有统计学意义(P=0.016)。PDLIM4高甲基化与患者血液学相关参数无明显相关性。PDLIM4启动子高甲基化频率随疾病进展而增高,在慢性期、加速期及急变期中分别为16%(7/44)、33%(2/6)及44%(4/9)。结论:PDLIM4基因启动子甲基化改变可能与CML的疾病发展有关。Objective： To analyze the expression transcript level and promoter hypermethylation of PDZ and LIM domain 4（PDLIM4） gene and the clinical correlations in Chinese patients with chronic myeloid leukemia（CML）.Methods： Real-time quantitative PCR（RQ-PCR） and real-time quantitative methylation-specific PCR（RQ-MSP） assays were used to detect the expression and methylation status of PDLIM4 gene in the bone marrow samples from CML patients.Results： Down-regulated PDLIM4 expression was found in 8/36（22%） CML cases,with significant statistical difference compared with all 21 controls（Fisher′s Exact Test,P=0.021）.There was a significant correlation between PDLIM4 expression and bcr/abl fusion transcript（r=0.434,P=0.043） in CML patients.Hypermethylation of PDLIM4 promoter was detected in 13/59（22%） CML patients,but not in all 24 controls（Fisher′s Exact Test,P=0.016）.PDLIM4 hypermethylation was not correlated with blood parameters（P0.05）.The frequencies of PDLIM4 promoter hypermethylation increased during the disease progression,as it was 16%（7/44）,33%（2/6） and 44%（4/9） in chronic phase,accelerated phase and blast crisis,respectively.Conclusion： Hypermethylation of PDLIM4 promoter may be associated with the disease progression in CML.

关 键 词：慢性髓系白血病 PDLIM4基因 表达 高甲基化 

分 类 号：R733.72[医药卫生—肿瘤]