Id4基因甲基化在急性白血病微量残留病检测中的意义

Id4 gene methylation for detection of minimal residual disease in acute leukemia

目的探讨 Id4基因甲基化作为检测急性白血病(AL)微量残留病变指标的可行性。方法采用甲基化特异性聚合酶链反应(MS-PCR)技术对细胞系中不同比例的白血病细胞以及正常人、初诊和完全缓解期的 AL 患者骨髓进行 Id4基因甲基化状态检测。结果 MS-PCR 方法可在低于1%白血病细胞中检测到Id4基因甲基化。Id4基因在正常骨髓中呈完全性非甲基化状态,初治急性髓系白血病(AML)和急性淋巴细胞白血病(ALL)患者中甲基化比例分别为84%和86%。Id4基因在完全缓解的 ALL 患者中甲基化比例达60.9%,高于完全缓解状态的 AML 患者。Id4基因甲基化检测阳性的14例 ALL 患者中有8例在12个月内复发,而甲基化检测阴性的9例 ALL 患者仅有1例复发。Id4基因呈甲基化状态的8例 AML 患者中有5例在12个月内复发,而 Id4基因呈非甲基化的20例 AML患者中12个月内仅有2例复发。结论 MS-PCR 检测 Id4基因甲基化有可能作为 AL 微量残留病的检测方法。

Objective To evaluate the possibility of Id4 gene promoter methylation as a biomarker for minima/residual disease （MRD） detection in acute leukemia. Methods Methylation specific-PCR technique was used to detect Id4 gene methylation in samples with different percentages of leukemia cells from leukemia cell line and bone marrows from leukemia patients in complete remission （CR）. Results Id4 gene methylation could be detected in samples containing 1% or lower leukemia cells. Frequency of Id4 gene methylation in acute lymphoblastic leukemia（ALL） patients in CR was 64.3% being higher than that in acute myeloid leukemia （AML） patients in CR. In 14 ALL patients with Id4 gene methylation, 8 relapsed in 12 months, while only one relapsed in 9 patients without Id4 gene methylation. In 8 AML patients with Id4 gene methylation, 5 relapsed in 12 months, while two relapsed in 20 AML patients with Id4 gene methylation. Conclusion Id4 gene promoter methylation is a candidate of biomarker for MRD detection in acute leukemias.