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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》2011年第1期76-80,共5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:为探讨zo-1基因甲基化状态改变在骨髓增生异常综合征(Myelodysplastic Syndrome MDS)与血液系统非恶性疾病鉴别诊断中的意义,采用甲基化特异性聚合酶链反应(methylation specific PCR,MS-PCR)及逆转录聚合酶链反应(reverse transcription-PCR,RT-PCR)检测MDS细胞系MUTZ1、1例再生障碍性贫血(aplastic anemia,AA)患者及正常供者的骨髓(normal bone marrow,NBM)。通过甲基化特异性聚合酶链反应(methylation specificPCR,MS-PCR),对37例MDS-RA患者、20例疑诊MDS患者及55例血液系统非恶性疾病患者骨髓标本进行检测。结果显示:①zo-1基因在MDS细胞系MUTZ1中呈完全甲基化且不表达,在1例AA患者骨髓及NBM中呈完全非甲基化且有表达;②zo-1基因在55例血液系统非恶性疾病患者骨髓标本中呈完全非甲基化状态,在MDS-RA患者骨髓中甲基化阳性率48.6%(18/37),二者差异有统计学意义(p<0.05);③20例疑似MDS患者中zo-1基因甲基化阳性率为35%(7/20)。随访甲基化阳性患者中的2例,均在1年内诊断为MDS。结论:MDS患者骨髓zo-1基因启动子区发生了高甲基化状态的改变,而血液系统良性疾病患者骨髓呈非甲基化状态。zo-1基因启动子区高甲基化在MDS患者骨髓标本中较特异,推测zo-1基因异常甲基化状态可能成为基因标志,它有助于MDS与AA等血液系统良性疾病的鉴别诊断,可应用于临床。It is hard to discriminate myelodysplastic syndrome(MDS)from many benign hematological diseases.To identify the methylation status of zo-1 gene in MDS,the methylation specific PCR(MS-PCR) and reverse transcription-PCR(RT-PCR) were applied to detect the MDS cell line MUTZ-1,bone marrow of a healthy donor and an aplastic anemia patient.MS-PCR was also employed to detect the bone marrow of 72 patients with benign hematological diseases,35 MDS-RA patients,and 20 MDS-like patients.The results showed that MDS cell line MUTZ-1 displayed complete methylation of zo-1 promoter without mRNA expression.Inversely,a patient with benign hematological disease and a donor with normal bone marrow showed complete unmethylation of this gene with unaffected mRNA expression.No zo-1 promoter methylation was detected in patients with benign hematological diseases,while aberrant hypermethylation of zo-1 gene promoter were found in 48.6 %(18/37) of MDS-RA patients.The positive rate of zo-1 methylation in MDS-RA patients was higher than that in patients with benign hematological diseases(p 0.05).Seven suspected MDS patients manifested hypermethylation status of zo-1 gene(7/20),2 were followed up for 1 year and transformed into MDS.It is concluded that relatively high hypermethylation rate of zo-1 promoter is observed in MDS-RA,and no methylation in patients with benign hematological diseases.Therefore,zo-1 gene hypermethylation may be served as a useful epigenetic marker in the differential diagnosis for MDS.
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