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急性髓系白血病E-cadherin基因表达和CpG岛甲基化状态的研究

Studies on gene expression and the 5’ CpG islands methylation status of E-cadherin in acute myeloid leukemia

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【作者】 高峰李艳刘巍卢香兰李霞王萍萍刘云鹏

【Author】 GAO Feng , LI Yan , LIU Wei, LU Xiang-lan, LI Xia, WANG Ping-ping, LIU Yun-peng. Department of Hematology, The First Affiliated Hospital, China Medical University, Shenyang 110001, China

【机构】 中国医科大学附属第一医院血液科中国医科大学附属第一医院血液科沈阳市沈河区人民医院中国医科大学附属第一医院肿瘤内科

【摘要】 目的探讨急性髓系白血病(AML)患者中上皮钙黏附素(E-cadherin)基因表达及其甲基化状态。方法分别用RT-PCR和流式细胞术方法检测55例AML患者骨髓细胞和7份正常对照骨髓细胞中E-cadherin基因和蛋白的表达,并用甲基化特异性PCR方法分析E-cadherin基因5’端CpG 岛的甲基化状况。结果 55例AML患者骨髓细胞中E-cadherin mRNA和蛋白表达阳性率分别为 23.6%和18.2%,较正常对照组明显下调(P值均<0.01);E-cadherin基因5’端甲基化的阳性率为 69.1%。E-cadherin mRNA和蛋白表达阴性的31例患者中,29例(93.5%)E-cadherin甲基化阳性,其蛋白水平和mRNA表达水平与启动子甲基化呈明显负相关(P<0.01)。7份正常对照骨髓细胞E-cad- herin mRNA和蛋白表达均为阳性,E-cadherin基因的CpG岛无明显甲基化。结论 AML的粒系分化成熟障碍可能与E-cadherin基因表达下调有关,5’端CpG岛的甲基化可能影响E-cadherin基因表达。

【Abstract】 Objective To study the relationship between E-cadherin gene expression and the methy-lation status of E-cadherin 5’ CpG islands in acute myeloid leukemia( AML). Methods Reverse transcription-PCR( RT-PCR) , flow cytometry and methylation specific PCR were used to analyze the E-cadherin gene and protein expression and its 5’ CpG island methylation status respectively in bone marrow cells from 55 AML patients and 7 normal controls. Results AML cells displayed a significant reduction or lack of E-cadherin gene and protein expression, the positive rates were 23. 6% and 18.2% (P<0.01), respectively. All normal bone marrow cells were E-cadherin positive. Thirty-eight of the 55 patients (69. 1% ) were E-cadherin 5’ CpG island methylated whereas the normal controls were completely unmethylated. Twenty-nine of thirty-one (93.5% ) E-cadherin-negative samples showed abnormal hypermethylation of the E-cadherin CpG islands. Conclusion Expression downregulation and methylation of E-cadherin gene in AML suggest that it might be an important event in AML. E-cadherin methylation was associated with the inhibition of E-cadherin gene and protein expression in AML.

【基金】 辽宁省科技攻关计划资助项目(2004225004-101)
  • 【文献出处】 中华血液学杂志 ,Chinese Journal of Hematology , 编辑部邮箱 ,2006年01期
  • 【分类号】R733.71
  • 【被引频次】11
  • 【下载频次】206
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