Hong Qingxiao, Chen Xiaoying, Ye Huadan, Zhou Annan, Gao Yuting, Jiang Danjie, Wu Xiaodong, Tian Bingru, Chen Youfen, Wang Ming, Xie Jiping, Xia Yongming, Duan Shiwei
Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
Department of Hematology, Yuyao People's Hospital, Yuyao, Zhejiang 315400, P.R. China.
Oncol Lett. 2016 Apr;11(4):2851-2856. doi: 10.3892/ol.2016.4317. Epub 2016 Mar 9.
The ) gene is a tumor suppressor gene that is associated with the risk of developing acute myeloid leukemia (AML). However, the association between the methylation status of the promoter and the chemotherapeutic outcomes of patients with AML remains unknown. In the present study, 30 bone marrow samples derived from patients with AML were collected prior and subsequent to chemotherapy. The methylation status of the MGMT promoter in the bone marrow specimens was determined by methylation-specific polymerase chain reaction. The results indicated that the methylation status of the MGMT promoter was influenced by different chemotherapeutic regimens. The MGMT methylation status of M4 patients (3 out of 6) were more chemosensitive, compared with that of patients with other AML subtypes (M1, 1 out of 3; M2, 0 out of 8; M3, 3 out of 7; M5, 0 out of 3; and M6, 1 out of 3). Age-based analysis revealed that the group aged ≤60 years (7 out of 24 patients) exhibited more methylation changes than patients aged >60 years (1 out of 6). Male patients (4 out of 13) were more susceptible to chemotherapy-induced methylation changes than female patients (4 out of 17). Thus, the methylation status of the MGMT promoter may serve as a potential biomarker to predict the therapeutic outcomes in male AML patients. However, further studies in larger sample sets are required to confirm the present findings.
)基因是一种肿瘤抑制基因,与急性髓系白血病(AML)的发生风险相关。然而,启动子的甲基化状态与AML患者化疗结果之间的关联仍不清楚。在本研究中,收集了30例AML患者化疗前后的骨髓样本。通过甲基化特异性聚合酶链反应测定骨髓标本中MGMT启动子的甲基化状态。结果表明,MGMT启动子的甲基化状态受不同化疗方案的影响。与其他AML亚型患者(M1,3例中的1例;M2,8例中的0例;M3,7例中的3例;M5,3例中的0例;M6,3例中的1例)相比,M4患者(6例中的3例)的MGMT甲基化状态对化疗更敏感。基于年龄的分析显示,年龄≤60岁的组(24例患者中的7例)比年龄>60岁的患者(6例中的1例)表现出更多的甲基化变化。男性患者(13例中的4例)比女性患者(17例中的4例)更容易受到化疗诱导的甲基化变化影响。因此,MGMT启动子的甲基化状态可能作为预测男性AML患者治疗结果的潜在生物标志物。然而,需要在更大样本量的研究中进一步证实本研究结果。