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Intragenic hypomethylation of DNMT3A in patients with myelodysplastic syndrome

  • Ying-Ying Zhang , Jing-Dong Zhou , Dong-Qin Yang , Pin-Fang He , Dong-Ming Yao , Zhen Qian , Jing Yang , Wen-Rong Xu , Jiang Lin EMAIL logo and Jun Qian EMAIL logo
Published/Copyright: October 14, 2017

Abstract

Background:

DNMT3A is a DNA methyltransferase that acts in de novo methylation. Aberrant expression of DNMT3A has been reported in several human diseases, including myelodysplastic syndrome (MDS). However, the pattern of DNMT3A methylation remains unknown in MDS.

Methods:

The present study was aimed to investigate the methylation status of DNMT3A intragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR and analyze its clinical significance in MDS.

Results:

Aberrant hypomethylation of DNMT3A was found in 57% (51/90) MDS cases. There were no significant differences in age, sex, white blood cell counts, platelet counts, hemoglobin counts and World Health Organization, International Prognostic Scoring System and karyotype classifications between DNMT3A hypomethylated and DNMT3A hypermethylated groups. However, the patients with DNMT3A hypomethylation had shorter overall survival time than those without DNMT3A hypomethylation (11 months vs. 36 months, p=0.033). Multivariate analysis confirmed the independent adverse impact of DNMT3A hypomethylation in MDS.

Conclusions:

Our data suggest that DNMT3A DMR2 hypomethylation may be a negative prognostic hallmark in MDS.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the National Natural Science foundation of China (81172592, 81270630), Special Funds of “Ke Jiao Qiang Wei” Project of Jiangsu Province, 333 Project of Jiangsu Province (BRA2016131), Six Talent Peaks Project in Jiangsu Province (2015-WSN-115), China Postdoctoral Science Foundation funded project (2016M601748), Social Development Foundation of Zhenjiang (SH2014044, SH2014086, SH2015058, SH2016045, SH2016046), Social Development Foundation of Kunshan (KS1624), Key Medical Talent Program of Zhenjiang City, Science and Technology Special Project in Clinical Medicine of Jiangsu Province (BL2012056) and Research and Development Foundation of Clinical Medicine of Jiangsu University (JLY20140018).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-2-22
Accepted: 2017-9-7
Published Online: 2017-10-14
Published in Print: 2018-2-23

©2018 Walter de Gruyter GmbH, Berlin/Boston

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