Intragenic hypomethylation of DNMT3A in patients with myelodysplastic syndrome

Author:

Zhang Ying-Ying12,Zhou Jing-Dong13,Yang Dong-Qin13,He Pin-Fang43,Yao Dong-Ming43,Qian Zhen13,Yang Jing13,Xu Wen-Rong5,Lin Jiang436,Qian Jun137

Affiliation:

1. Department of Hematology , Affiliated People’s Hospital of Jiangsu University , Zhenjiang, Jiangsu , P.R. China

2. Department of Hematology and Oncology , Yizheng People’s Hospital , Yangzhou, Jiangsu , P.R. China

3. The Key Laboratory of Precision Diagnosis and Treatment of Zhenjiang City , Zhenjiang, Jiangsu , P.R. China

4. Laboratory Center , Affiliated People’s Hospital of Jiangsu University , Zhenjiang, Jiangsu , P.R. China

5. Key Laboratory of Laboratory Medicine of Jiangsu Province , Medical Key Talent Project of Zhenjiang , Zhenjiang , P.R. China

6. Laboratory Center , Affiliated People’s Hospital of Jiangsu University , 8 Dianli Rd. , 212002 Zhenjiang , P.R. China , Fax: +86.511.85234387

7. Department of Hematology , Affiliated People’s Hospital of Jiangsu University , 8 Dianli Rd. , 212002 Zhenjiang , P.R. China , Fax: +86.511.85234387

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Biochemistry, medical,Clinical Biochemistry,General Medicine

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