Research Paper Volume 12, Issue 6 pp 5031—5047

Expression and prognosis analysis of TET family in acute myeloid leukemia

Tingjuan Zhang 1, 2, 3, 4, *, , Yangli Zhao 2, 5, *, , Yangjing Zhao 6, , Jingdong Zhou 1, 2, 3, 4, ,

  • 1 Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
  • 2 Zhenjiang Medical School, Nanjing Medical University, Zhenjiang, Jiangsu, People’s Republic of China
  • 3 Zhenjiang Clinical Research Center of Hematology, Zhenjiang, Jiangsu, People’s Republic of China
  • 4 The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang, Zhenjiang, Jiangsu, People’s Republic of China
  • 5 Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
  • 6 Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
* Equal contribution

received: December 30, 2019 ; accepted: March 4, 2020 ; published: March 25, 2020 ;

https://doi.org/10.18632/aging.102928
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

TET family members (TETs) encode proteins that represent crucial factors in the active DNA demethylation pathway. Evidence has proved that TET2 mutation is associated with leukemogenesis, drug response, and prognosis in acute myeloid leukemia (AML). However, few studies revealed the TETs expression and its clinical significance in AML. We conducted a detailed expression and prognosis analysis of TETs expression in human AML cell lines and patients by using public databases. We observed that TETs expression especially TET2 and TET3 was closely associated with AML among various human cancers. TET1 expression was significantly reduced in AML patients, whereas TET2 and TET3 expression was significantly increased. Kaplan-Meier analysis showed that only TET3 expression was associated with overall survival (OS) and disease-free survival (DFS) among both total AML as well as non-M3 AML, and was confirmed by another independent cohort. Moreover, Cox regression analysis revealed that TET3 expression may act as an independent prognostic factor for OS and DFS in total AML. Interestingly, patients that received hematopoietic stem cell transplantation (HSCT) did not show significantly longer OS and DFS than those who did not receive HSCT in TET3 high-expressed groups; whereas, in TET3 low-expressed groups, patients that accepted HSCT showed significantly longer OS and DFS than those who did not accept HSCT. By bioinformatics analysis, TET3 expression was found positively correlated with tumor suppressor gene including CDKN2B, ZIC2, miR-196a, and negatively correlated with oncogenes such as PAX2 and IL2RA. Our study demonstrated that TETs showed significant expression differences in AML, and TET3 expression acted as a potential prognostic biomarker in AML, which may guide treatment choice between chemotherapy and HSCT.

Abbreviations

AML: acute myeloid leukemia; DNMTs: DNA methyltransferases; TET: Ten-eleven translocation; MDS: myelodysplastic syndromes; CMML: chronic myelomonocytic leukemia; CN-AML: cytogenetically normal AML; TCGA: The Cancer Genome Atlas; CCLE: Cancer Cell Line Encyclopedia; HPA: The Human Protein Atlas; EMBL-EBI: European Bioinformatics Institute; GEPIA: Gene Expression Profiling Interactive Analysis; GTEx: Genotype-Tissue Expression; WBC: white blood cell; PB: peripheral blood; BM: bone marrow; FAB: French-American-British; HSCT: hematopoietic stem cell transplantation; DFS: disease-free survival; OS: overall survival; CN-AML: cytogenetically normal AML.