Zo-1与id4基因异常甲基化在多发性骨髓瘤中的临床意义  

Clinical Significance of zo-1 and id4 Gene Abnormal Methylation in Multiple Myeloma

作　　者：康慧媛[1] 王新荣[1] 王莉莉[1] 王畅[1,2] 岑坚[1,3] 高丽[1] 刘洋[1,4] 李永辉[1] 于力[1] 

机构地区：[1]中国人民解放军总医院血液科,北京100853 [2]吉林大学第一医院血液肿瘤科,吉林长春130021 [3]海军总医院血液科,北京100037 [4]中国人民解放军总医院老年血液科,北京100853

出　　处：《中国实验血液学杂志》2010年第5期1192-1197,共6页Journal of Experimental Hematology

基　　金：973国家重点基础研究专项经费项目(编号2005CB522400);国家自然科学基金重大研究计划(编号90919044);首度医学发展科研基金重点项目(编号2007-2040)

摘　　要：多发性骨髓瘤(multiple myeloma,MM)是浆细胞恶性增殖性疾病,常规化疗不能治愈,为探讨zo-1、id4基因异常甲基化在MM诊断、预后、微小残留病检测及治疗中基因标志作用的临床意义,采用甲基化特异性聚合酶链反应(methylation specific PCR,MS-PCR)方法检测MM细胞系U266、H929及IM9(B淋巴母细胞,MM患者骨髓来源)中zo-1、id4基因的甲基化状况;应用MS-PCR方法分析20例MM患者及6例健康供者骨髓标本zo-1、id4基因启动子区甲基化状况。结果显示:zo-1、id4基因在MM细胞系中均为甲基化阳性(完全甲基化或部分甲基化);zo-1、id4基因在5例健康人标本中均呈完全非甲基化状态;MM患者骨髓中zo-1、id4基因甲基化阳性率分别是50%和85%,二者阳性覆盖率高达95%,二者均阳性的标本阳性率为40%,明显高于健康人(0%),差异均有统计学意义(p<0.05);MM患者不同重链及不同轻链间甲基化阳性率没有统计学差异;MM患者是否具有B组症状并不影响患者的甲基化阳性率,这可能与标本数量有关。结论:MM患者中zo-1、id4基因甲基化状态发生改变并具有特异性,可能是MM新的基因标记。Multiple myeloma（MM） is an incurable heterogeneous disease derived from malignant clonal expansion of plasma cells.The evaluation of prognosis,detection of minimal residual disease（MRD） and treatment of MM are unclear for decades.Recently,Valcade and autotransplantation have been broadly applied to MM patients and achieved better outcomes,but there is yet no effective and universal marker for MRD detection in MM.Both genetic and epigene-tic aberrations play important roles in the pathogenesis and development of cancer.Our preliminary data showed that aberrant promoter methylation of zo-1 and id4 genes was correlated with their gene silencing in several types of hematological malignancies.Therefore,this study was aimed to identify the promoter methylation status of zo-1 and id4 genes in MM and their relationship with the prognosis,MRD and treatment of MM.The methylation status of zo-1 and id4 genes of MM cell lines U266,H929 and IM9 was tested by using MS-PCR;the methylation status of zo-1,id4 gene promoters in bone marrow samples of 20 MM patients and 6 healthy persons was detected by MS-PCR.The results showed that the zo-1,id4 gene in MM cell lines all were methylation positive（complete or partial methylation）,the zo-1,id4 gene in samples of 5 healthy persons all were completely unmethylated. The methylation positive rate of zo-1 and id4 genes were 50% and 85% respectively,which were significantly higher than that in normal bone marrow（0%）.The coverage rate of zo-1 and id4 gene mathylation was 95%.There were no significant differences in the methylation status of both genes among the patients with different heavy chains,different light chains and symptoms.It is concluded that the change of zo-1,id4 genes methylation status occurs in MM patients and has specificity,which may be a new gene marker of MM,methylation analysis of zo-1 and id4 genes may be important for MRD monitoring in patients with MM.

关 键 词：ZO-1基因 ID4基因 基因甲基化 多发性骨髓瘤 

分 类 号：R733.3[医药卫生—肿瘤]