单位：[1]Department of Oncology, Chinese PLAGeneral Hospital,[2]Department of Hematology, China-Japan Friendship Hospital,[3]Department of Geriatric Medicine, Army General Hospital, Beijing, People’s Republic of China
Objective: The purpose of this study was to evaluate the frequency of RASSF1A hypermethylation in patients with acute myeloid leukemia (AML), in an attempt to modify the current molecular model for disease prognosis. Materials and methods: Aberrant RASSF1A promoter methylation levels were assessed in 226 newly diagnosed non-M3 AML patients and 30 apparently healthy controls, by quantitative methylation-specific polymerase chain reaction. Meanwhile, RASSF1A mRNA levels were detected by real-time quantitative polymerase chain reaction. Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic aberrations were assessed. Finally, associations of RASSF1A hypermethylation with clinical outcomes were evaluated. Results: RASSF1A hypermethylation was observed in 23.0% of patients with non-M3 AML (52/226), but not in controls. Meanwhile, hypermethylation of the RASSF1A promoter was significantly associated with ASXL1 mutation. Furthermore, the log-rank test revealed that RASSF1A hypermethylation indicated decreased relapse-free survival (RFS) and overall survival (OS) in patients with non-M3 AML (P=0.012 and P=0.014, respectively). In multivariate analysis, RASSF1A hypermethylation was an independent prognostic factor for RFS (P=0.040), but not for OS (P=0.060). Conclusion: Hypermethylation of the RASSF1A promoter is associated with ASXL1 mutation in non-M3 AML patients, likely indicating poor outcome. These findings provide a molecular basis for stratified diagnosis and prognostic evaluation.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81300425, 81300450]; Key Program of Capital Development Foundation [2007-2040]
第一作者单位：[1]Department of Oncology, Chinese PLAGeneral Hospital,[*2]Department of Oncology, Chinese PLAGeneral Hospital, Fuxing Road, Beijing, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology, Chinese PLAGeneral Hospital,[2]Department of Hematology, China-Japan Friendship Hospital,[*1]Department of Hematology, China-Japan Friendship Hospital, East Yinghua Road, Beijing, People’s Republic of China[*2]Department of Oncology, Chinese PLAGeneral Hospital, Fuxing Road, Beijing, People’s Republic of China
推荐引用方式(GB/T 7714)：
Liu Fang,Gong Ming,Gao Li,et al.RASSFIA hypermethylation is associated with ASXLI mutation and indicates an adverse outcome in non-M3 acute myeloid leukemia[J].ONCOTARGETS and THERAPY.2017,10:4143-4151.doi:10.2147/OTT.S142528.
APA：
Liu, Fang,Gong, Ming,Gao, Li,Cai, Xiaoping,Zhang, Hui&Ma, Yigai.(2017).RASSFIA hypermethylation is associated with ASXLI mutation and indicates an adverse outcome in non-M3 acute myeloid leukemia.ONCOTARGETS and THERAPY,10,
MLA：
Liu, Fang,et al."RASSFIA hypermethylation is associated with ASXLI mutation and indicates an adverse outcome in non-M3 acute myeloid leukemia".ONCOTARGETS and THERAPY 10.(2017):4143-4151
