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RASSF1A hypermethylation is associated with ASXL1 mutation and indicates an adverse outcome in non-M3 acute myeloid leukemia

Authors Liu F, Gong M, Gao L, Cai X, Zhang H, Ma Y

Received 24 May 2017

Accepted for publication 20 July 2017

Published 22 August 2017 Volume 2017:10 Pages 4143—4151


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

Fang Liu,1,* Ming Gong,2,* Li Gao,2,* Xiaoping Cai,3 Hui Zhang,2 Yigai Ma2

1Department of Oncology, Chinese PLA General Hospital, 2Department of Hematology, China-Japan Friendship Hospital, 3Department of Geriatric Medicine, Army General Hospital, Beijing, People’s Republic of China

*These authors contributed equally to this work

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.

Keywords: RASSF1A, hypermethylation, acute myeloid leukemia, clinical outcome, survival

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