Research Paper Advance Articles

Expression and prognosis analysis of DNMT family in acute myeloid leukemia

Ting-Juan Zhang1,2,3, , Liu-Chao Zhang4, *, , Zi-Jun Xu2,3,5, *, , Jing-Dong Zhou1,2,3, ,

  • 1 Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, JiangsuPeople’s Republic of China
  • 2 Zhenjiang Clinical Research Center of Hematology, Zhenjiang, Jiangsu, People’s Republic of China
  • 3 The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang, Zhenjiang, Jiangsu, People’s Republic of China
  • 4 Department of Medical Laboratory, Shanghai Deji Hospital, Qingdao University, Shanghai, People’s Republic of China
  • 5 Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
* Equal contribution

Received: March 24, 2020       Accepted: June 4, 2020       Published: June 26, 2020      

https://doi.org/10.18632/aging.103520
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

DNA methyltransferases (DNMTs) by regulating DNA methylation play crucial roles in the progression of hematologic malignancies, especially for acute myeloid leukemia (AML). Accumulating investigations have identified the high incidence of DNMT3A mutation in AML, and it is correlated with poor prognosis. Although a few studies have shown the expression of DNMTs and their clinical significance in AML, the results remain to be discussed. Herein, we systemically analyzed the DNMTs expression and their relationship with clinic-pathological features and prognosis in AML patients. DNMTs expression especially for DNMT3A/3B was closely associated with AML among various human cancers. DNMT3A expression was increased in AML patients, whereas DNMT3B expression was decreased. Significant associations between DNMT3A/B expression and clinic-pathological features/gene mutations were observed. Kaplan-Meier analysis showed that DNMT3A expression was associated with better overall survival (OS) and leukemia-free survival (LFS) among whole-cohort AML, and independently affected OS determined by Cox repression multivariate analysis. Notably, patients that received hematopoietic stem cell transplantation (HSCT) showed significantly better OS and LFS in DNMT3A lower-expressed groups, whereas patients in DNMT3A higher-expressed groups did not. By bioinformatics analysis, DNMT3A expression was found to be positively correlated with several leukemia-associated genes/microRNAs, and DNMT3A was identified as direct targets of miR-429 and miR-29b in AML. Collectively, our study demonstrated that DNMT3A/3B showed significant expression differences in AML. DNMT3A expression acted as a potential prognostic biomarker and may guide treatment choice between chemotherapy and HSCT in AML.

Abbreviations

TSGs: tumor suppressor genes; AML: acute myeloid leukemia; MDS: myelodysplastic syndromes; HMAs: hypomethylating agents; DNMTs: DNA methyltransferases; LSC: leukemia stem cell; HSC: hematopoietic stem cell; CCLE: Cancer Cell Line Encyclopedia; HPA: The Human Protein Atlas; EMBL-EBI: European Bioinformatics Institute; GEPIA: Gene Expression Profiling Interactive Analysis; TCGA: The Cancer Genome Atlas; GTEx: The Genotype-Tissue Expression; WBC: white blood cells; PB: peripheral blood; BM: bone marrow; FAB: French-American-British; HSCT: hematopoietic stem cell transplantation; CN-AML: cytogenetically normal AML; OS: overall survival; LFS: leukemia-free survival; DEGs: differentially expressed genes; GO: Gene Ontology.