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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
【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.
【Key words】 Leukemia, nonlymphocytic, acute; Gene, E-cadherin; DNA methylation; CpG islands;
- 【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