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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。
Objective To investigate the gene expression of E-cadherin and its methylation status in patients with acute myeloid leukemia (AML). Methods The expression of E-cadherin gene and protein in bone marrow cells from 55 AML patients and 7 normal control bone marrow cells were detected by RT-PCR and flow cytometry. Methylation-specific PCR was used to analyze the expression of E-cadherin gene 5 CpG island methylation status. Results The positive rates of E-cadherin mRNA and protein in 55 AML patients were 23.6% and 18.2%, respectively, which were significantly lower than those in normal controls (all P <0.01). E-cadherin gene 5 The positive rate of methylation was 69.1%. Of the 31 patients with negative E-cadherin mRNA and protein expression, 29 (93.5%) had positive methylation of E-cadherin, and their protein levels and mRNA expressions were negatively correlated with promoter methylation (P < 0.01). The mRNA and protein expressions of E-cadherin in 7 normal control bone marrow cells were all positive, and the CpG island of E-cadherin gene was not methylated. Conclusion The maturation of granulocytic differentiation in AML may be related to the down-regulation of E-cadherin gene expression. The methylation of 5 ’CpG island may affect the expression of E-cadherin gene.