Chemotherapy‑induced hypomethylation of N‑myc downstream‑regulated gene 4 in the bone marrow of patients with acute myeloid leukemia

Hong,Qingxiao; Chen,Xiaoying; Ye,Huadan; Wu,Xiaodong; Wang,Xuejing; Kong,Lingyan; Xia,Yongming; Duan,Shiwei

doi:10.3892/ol.2017.5839

Chemotherapy‑induced hypomethylation of N‑myc downstream‑regulated gene 4 in the bone marrow of patients with acute myeloid leukemia

Authors:
- Qingxiao Hong
- Xiaoying Chen
- Huadan Ye
- Xiaodong Wu
- Xuejing Wang
- Lingyan Kong
- Yongming Xia
- Shiwei Duan
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Affiliations: 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
Published online on: March 10, 2017 https://doi.org/10.3892/ol.2017.5839
Pages: 3309-3313

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Abstract

N‑myc downstream‑regulated gene 4 (NDRG4) 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 NDRG4 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 NDRG4 gene were measured using bisulfite pyrosequencing techniques. The results indicated significantly reduced gene‑body methylation levels of NDRG4 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 NDRG4 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 NDRG4 gene‑body in patients with AML (particularly patients with M2 subtype AML) during chemotherapy.

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