ZO-1基因甲基化在MDS进展中的意义

Clinical Implications on ZO-1 Gene Methylation in Myelodysplastic Syndrome Progression

目的:探讨ZO-1基因甲基化在骨髓增生异常综合征(myelodysplastic syndrome,MDS)向急性髓系白血病(acute myeloid leukemia,AML)转化中的临床意义,为MDS患者的预后评估进一步提供理论依据。方法:采用甲基化特异性PCR(methylation specific PCR,MS-PCR)方法检测ZO-1基因在正常对照者骨髓标本(normal control,NC)、MDS、AML患者骨髓标本中的甲基化状态。运用亚硫酸氢盐侧序PCR(bisulfite sequencing PCR,BSP)方法检测1例MDS系列标本ZO-1基因在其MDS-RA、MDS-RAEB、AML阶段的甲基化状态。结果:ZO-1基因在NC、MDS、AML患者标本中的甲基化阳性率存在明显差异(P=0.000),在NC组未发现甲基化阳性,在AM L组阳性率最高(65.0%)。MDS/AML患者ZO-1基因甲基化阳性组髓系原始细胞比例更高(P=0.000)。1例MDS患者系列标本显示,随着疾病进展,在MDS-RA、MDS-RAEB、AML阶段中,甲基化位点阳性频率存在明显差异(P=0.000),在AML阶段阳性频率最高(64.65%)。结论:ZO-1基因启动子区高甲基化发生于MDS/AML患者中,随着恶性克隆增生,ZO-1基因甲基化阳性率及甲基化位点阳性频率越来越高,在一定程度上预示着MDS疾病进展,进一步提示ZO-1基因甲基化水平可成为监测MDS患者急性白血病转化的新指标。

Objective： To investigate the clinical significance of ZO-1 gene methylation level in MDS progression in order to provide a theoretical basis for evaluating progrosis of MDS patients. Methods：The methylation specific PCR （MS-PCR） was performed to evaluate the ZO-1 gene methylation status in bone marrow samples of normal persons as control （NC）. MDS and AML patients, the bisulfite sequencing PCR （BSP） was applied to detect the ZO-1 gene methylation status in serial bone marrow samples of MDS-RA, MDS-RAEB and AML stages of a MDS patients. Results： The possitive rate of ZO-1 gene methylation in samples of NC, MDS and AML patients displayed significant difference ; in sample of NC group the positive of ZO-1 gene methylation was not observed, but the positive rate of ZO- 1 gene methylation in samples of AML patients was highest （65.0%）, the proportion of ZO-1 gene methylation in myeloid blast count of MDS/AML patients was higher （ P = 0.000 ）. The serial samples in one MDS patient showed that along with progress of disease, the positive rate of ZO-1 gene methylation in MDS-RA, MDS-RAEB and AML stages was found to be obvious different （ P = 0. 000 ）, the positive rate of ZO-1 gene methylation in AML stage was highest （64.65%）. Conclusion： The high methylation in promoter region of ZO-1 gene has been found in MDS/AML patients, and along with clonal proliferation, the positive rate of ZO-1 methylation and positive froguency of methylation sites increase graduatly which suggests that the MDS progresses in a certain degree, and the ZO-1 gene methylation level may be used as an new indicator for monitoring desease progression from MDS to AML.