急性白血病ZO-1基因启动子区甲基化状态分析及其临床意义

The methylation pattern and clinical significance of Zonula occludens-1 gene promoter in acute leukemia

目的探讨紧密连接蛋白-1（Zonula oecludem-1，ZO-1）基因启动子区甲基化状态在人急性白血病（AL）发生、发展中的作用及作为通用性基因标志物的临床意义。方法应用甲基化特异性聚合酶链反应（MS-PCR）检测白血病细胞系HL60、Molt4、NK92和40例非恶性血液病以及81例AL骨髓ZO-1基因启动子区的甲基化状态。结果ZO-1基因启动子区在白血病细胞系中呈完全甲基化状态；而在40例非恶性血液病标本中均为非甲基化；81例AL标本中甲基化阳性率为60．49％（49／81），其中难治复发组为92．86％（13／14），高于初诊未治疗组65．85％（27／41）及完全缓解组34．62％（9／26）；急性髓细胞白血病组61．54％（32／52）与急性淋巴细胞白血病组58．62％（17／29）比较差异无统计学意义。结论首次证明ZO-1基因启动子区高甲基化状态在人AL中具有较高的特异性，与疾病发生、发展密切相关，可作为一个新的白血病通用分子标志。

Objective To investigate the methylation status of Zonula occludens-1 （ZO-1） gene promoter and discuss its role in the pathogenesis and progression of acute leukemia （AL） as a general gene marker. Methods The methylation pattern in promoter region of ZO-1 gene was detected with methylation specific PCR in AL cell lines HL60, Molt4 and NK92 as well as in 121 clinical bone marrow samples including 81 cases of AL and 40 non malignant cases. Results The promoter region of ZO-1 gene was completely methylated in HL60, Moh4 and NK92 cells; but it was unmethylated in 40 non malignant bone marrow samples. The total methylation frequency of ZO-1 gene promoter region in 81 cases of AL was 60.49% （49/81）, there was significant statistic difference among the relapsed AL group （92.86%, 13/14）, the newly diagnosed AL group （65. 85% , 27/41 ） and the complete remission group （34. 62% , 9/26）, but no difference between the eases with acute myelocytie leukemia and acute lymphocytic leukemia. Conclusion The hypermethylated status of ZO-1 gene promoter region was specifically detected in human AL, it was closely correlated with the pathogenesis and progression of the disease and will become a general clinical molecular marker of leukemia.