Hong Qingxiao, Chen Xiaoying, Ye Huadan, Wu Xiaodong, Wang Xuejing, Kong Lingyan, Xia Yongming, Duan Shiwei
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. 2017 May;13(5):3309-3313. doi: 10.3892/ol.2017.5839. Epub 2017 Mar 10.
N-myc downstream-regulated gene 4 () has previously been investigated as a possible tumor suppressor. Hypermethylation of tumor suppressor genes contributes to the occurrence and development of certain types of cancer, including acute myeloid leukemia (AML). The current study aimed to assess the contribution of chemotherapy-induced changeable methylation to the development of AML. A total of 30 patients (13 males and 17 females) were involved in the present study. The DNA methylation levels of five C-phosphate-G sites of the gene were measured using bisulfite pyrosequencing techniques. The results indicated significantly reduced gene-body methylation levels of during chemotherapy (prior to chemotherapy: 9.35±4.22%; following chemotherapy: 7.54±3.11%; P=0.030). Further analysis of AML subtypes revealed the methylation reductions were principally contributed by patients with M2 subtype AML (prior to chemotherapy: 9.91±4.76%; following chemotherapy: 5.26±1.16%; P=0.038). A significant association was also observed between the patient age and the altered levels of gene-body methylation in patients with M2 subtype AML (r=0.761; P=0.047), suggesting that reductions in induced-methylation may be age-dependent in patients with M2 subtype AML during chemotherapy. Therefore, age may affect the induced methylation levels of gene-body in patients with AML (particularly patients with M2 subtype AML) during chemotherapy.
N-myc下游调控基因4（）此前已被作为一种可能的肿瘤抑制因子进行研究。肿瘤抑制基因的高甲基化促成了某些类型癌症的发生和发展，包括急性髓系白血病（AML）。当前研究旨在评估化疗诱导的可变甲基化对AML发展的作用。本研究共纳入30例患者（13例男性和17例女性）。使用亚硫酸氢盐焦磷酸测序技术测量该基因五个C-磷酸-G位点的DNA甲基化水平。结果表明化疗期间该基因的基因体甲基化水平显著降低（化疗前：9.35±4.22%；化疗后：7.54±3.11%；P = 0.030）。对AML亚型的进一步分析显示，甲基化降低主要由M2亚型AML患者导致（化疗前：9.91±4.76%；化疗后：5.26±1.16%；P = 0.038）。在M2亚型AML患者中还观察到患者年龄与基因体甲基化水平改变之间存在显著关联（r = 0.761；P = 0.047），这表明在化疗期间M2亚型AML患者中诱导甲基化的降低可能与年龄有关。因此，年龄可能会影响化疗期间AML患者（特别是M2亚型AML患者）基因体的诱导甲基化水平。
