急性白血病Id4基因启动子区甲基化状态研究

Methylation of Id4 Gene Promoter in Acute Leukemia

本研究探讨正常人和不同疾病状态急性白血病(AL)患者Id4基因启动子区甲基化状态差异。采用甲基化特异性聚合酶链反应(MS-PCR)对正常人和AL患者骨髓进行Id4基因启动子区甲基化状况检测。结果表明:Id4基因在正常骨髓中呈完全性非甲基化状态,初治AML和ALL患者中Id4基因甲基化比例分别为84%和86%。8例复发难治的AL患者中Id4基因全部甲基化,14例Id4基因甲基化的完全缓解ALL患者中有8例在12个月内复发,而9例Id4基因非甲基化的完全缓解ALL患者中12月内复发仅1例;Id4基因呈甲基化状态的完全缓解的AML患者中12个月内复发率为62.5%,而在非甲基化的患者中12个月内复发率仅为10%,两者差异有显著性意义。完全缓解的ALL患者甲基化比例为64.3%,而完全缓解的AML患者甲基化比例为28.6%,两者差异有显著性意义。39例初治AL中,有33例Id4基因呈甲基化状态,8例复发难治的AL患者的Id4基因均呈甲基化状态,58例完全缓解的AL中,有24例Id4基因呈甲基化状态。结论:与正常人不同,AL患者中Id4基因都发生了不同程度的甲基化改变,缓解状态患者的甲基化比例低于非缓解状态患者,Id4基因甲基化模式的改变与AL的发生密切相关。

This study was purposed to investigate the difference of Id4 gene promoter methylation between healthy individuals and acute leukemia patients. MS-PCR methods were used to detect the status of Id4 gene methylation in healthy individuals and acute leukemia patients. The results showed that Id4 gene was unmethylated in bone marrow samples from healthy individuals. In new diagnosed AML and ALL patients, the rate of Id4 gene methylation was 84% and 86% respectively. Id4 gene methylation was found in all 8 cases of relapsed acute leukemias. In 14 ALL-CR patients with Id4 gene methylation, 8 patients relapsed within 12 months, while in 9 ALL-CR patients with Id4 gene unmethylation only l patient relapsed within 12 months. In AML-CR patients, the 12-months relapse rate in patients with Id4 gene methylation was 62.5%, while it was 10% in Id4 gene unmethylation patients, there was significant difference between them. The rate of Id4 gene methylation in ALL-CR patients was 64.3% ,while it was 28.6% in AML-CR patients, there was significant difference between them. In the all 39 new diagnosed AL patients, Id4 gene methylation could be detected in 33 patients. In all 8 relapsed AL patients Id4 gene methylation was found, out of 58 AL-CR cases, 24 patients was found with Id4 gene methylation. It is concluded that as compared with healthy individuals, Id4 gene in acute leukemia patients was methylated in different degrees. The percentage of Id4 gene methylation in AL-CR group is lower than that in AL- non remission group. The change of Id4 gene methylation is thought to be associated with occurence of acute leukemia.