Association between the methylation status of the MGMT promoter in bone marrow specimens and chemotherapy outcomes of patients with acute myeloid leukemia

被引:16
作者
Hong, Qingxiao [1 ]
Chen, Xiaoying [1 ]
Ye, Huadan [1 ]
Zhou, Annan [1 ]
Gao, Yuting [1 ]
Jiang, Danjie [1 ]
Wu, Xiaodong [2 ]
Tian, Bingru [2 ]
Chen, Youfen [2 ]
Wang, Ming [2 ]
Xie, Jiping [2 ]
Xia, Yongming [2 ]
Duan, Shiwei [1 ]
机构
[1] Ningbo Univ, Sch Med, Dept Biochem & Mol Biol, Zhejiang Prov Key Lab Pathophysiol, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China
[2] Yuyao Peoples Hosp, Dept Hematol, 800 Chengdong Rd, Yuyao 315400, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
acute myeloid leukemia; chemotherapy; promoter; methylation; MGMT; MYELODYSPLASTIC SYNDROME; ABERRANT METHYLATION; CELLS; RISK; TEMOZOLOMIDE; CANCER;
D O I
10.3892/ol.2016.4317
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The O(6)-methylguanine-DNA methyltransferase (MGMT) 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 MGMT 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.
引用
收藏
页码:2851 / 2856
页数:6
相关论文
共 20 条
[1]   Gene silencing by DNA methylation in haematological malignancies [J].
Boultwood, Jacqueline ;
Wainscoat, James S. .
BRITISH JOURNAL OF HAEMATOLOGY, 2007, 138 (01) :3-11
[2]   Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O6-methylguanine DNA methyltransferase expression [J].
Brandwein, Joseph M. ;
Kassis, Jeannine ;
Leber, Brian ;
Hogge, Donna ;
Howson-Jan, Kang ;
Minden, Mark D. ;
Galarneau, Andre ;
Pouliot, Jean-Francois .
BRITISH JOURNAL OF HAEMATOLOGY, 2014, 167 (05) :664-670
[3]   Hypermethylation of EDNRB promoter contributes to the risk of colorectal cancer [J].
Chen, Cheng ;
Wang, Lingyan ;
Liao, Qi ;
Huang, Yi ;
Ye, Huadan ;
Chen, Fei ;
Xu, Leiting ;
Ye, Meng ;
Duan, Shiwei .
DIAGNOSTIC PATHOLOGY, 2013, 8
[4]  
Davis AS, 2014, AM FAM PHYSICIAN, V89, P731
[5]   Acute myeloid leukemia: 2013 update on risk-stratification and management [J].
Estey, Elihu H. .
AMERICAN JOURNAL OF HEMATOLOGY, 2013, 88 (04) :317-327
[6]   Frequency and Prognostic Impact of CEBPA Proximal, Distal and Core Promoter Methylation in Normal Karyotype AML: A Study on 623 Cases [J].
Fasan, Annette ;
Alpermann, Tamara ;
Haferlach, Claudia ;
Grossmann, Vera ;
Roller, Andreas ;
Kohlmann, Alexander ;
Eder, Christiane ;
Kern, Wolfgang ;
Haferlach, Torsten ;
Schnittger, Susanne .
PLOS ONE, 2013, 8 (02)
[7]   DNA repair mechanisms in dividing and non-dividing cells [J].
Iyama, Teruaki ;
Wilson, David M., III .
DNA REPAIR, 2013, 12 (08) :620-636
[8]  
Johannes Z, 2009, GENE DEV, V23, p877 889, DOI [10.1101/gad.177140919339691, DOI 10.1101/GAD.177140919339691]
[9]   Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells [J].
Kurtovic, Nada Kraguljac ;
Krajnovic, Milena ;
Bogdanovic, Andrija ;
Suvajdzic, Nada ;
Jovanovic, Jelica ;
Dimitrijevic, Bogomir ;
Colovic, Milica ;
Krtolica, Koviljka .
MEDICAL ONCOLOGY, 2012, 29 (05) :3547-3556
[10]   Gene regulation by SMAR1: Role in cellular homeostasis and cancer [J].
Malonia, Sunil Kumar ;
Sinha, Surajit ;
Lakshminarasimhan, Pavithra ;
Singh, Kamini ;
Jalota-Badhwar, Archana ;
Rampalli, Shravanti ;
Kaul-Ghanekar, Ruchika ;
Chattopadhyay, Samit .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2011, 1815 (01) :1-12