Lower Levels of TET2 Gene Expression, with a Higher Level of TET2 Promoter Methylation in Patients with AML; Evidence for the Role of Aberrant Methylation in AML Pathogenesis

Bahare Ghasemi; Javad Ahmadi; Farhad Zaker; Tahere Tabatabaei; Masoumeh Kiani-Zadeh; Ahmad Kazemi

doi:10.1007/s12288-023-01673-y

Lower Levels of TET2 Gene Expression, with a Higher Level of TET2 Promoter Methylation in Patients with AML; Evidence for the Role of Aberrant Methylation in AML Pathogenesis

Indian J Hematol Blood Transfus. 2024 Jan;40(1):52-60. doi: 10.1007/s12288-023-01673-y. Epub 2023 Jun 5.

Authors

Bahare Ghasemi^#¹, Javad Ahmadi^#², Farhad Zaker¹, Tahere Tabatabaei¹, Masoumeh Kiani-Zadeh¹, Ahmad Kazemi¹

Affiliations

¹ Present Address: Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
² Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.

^# Contributed equally.

PMID: 38312186
PMCID: PMC10831019 (available on 2025-01-01)
DOI: 10.1007/s12288-023-01673-y

Abstract

DNA methylation is a key epigenetic mechanism that is dysregulated in leukemia and plays a significant role in leukemogenesis. Ten-eleven translocation 2 (TET2) is one of the most frequently mutated genes among the DNA methylation regulators in hematologic malignancies, indicating its tumor-suppressor function. In this study, we investigated the expression and methylation status of TET2 in patients with AML. Quantitative RT-PCR was used to evaluate TET2 expression in peripheral blood mononuclear cells (PBMCs) from 51 newly diagnosed AML patients and 50 healthy controls. The methylation-sensitive high-resolution melting (MS-HRM) method was used in 45 patients with AML and 15 healthy controls to evaluate the promoter methylation of TET2. TET2 expression was significantly downregulated (P < 0.0001) in patients with AML compared to that in healthy controls. Furthermore, the methylation level of the TET2 promoter was significantly different between patients and controls. Aberrant methylation of the TET2 promoter was observed in 53.3% of the patients. Interestingly, a negative (- 0.3138) and significant (P = 0.0358) correlation between TET2 methylation and expression was found. The survival of patients with downregulated TET2 was poorer than that of other patients. TET2 gene expression was significantly downregulated while the promoter methylation was higher in patients, indicating that TET2 may be a tumor suppressor gene and a prognostic factor in AML and that transcriptional silencing of the TET2 gene may play a role in AML pathogenesis. Since epigenetic mechanisms are reversible, abnormal TET2 methylation could become a therapeutic target in the future.

Keywords: Acute myeloid leukemia; DNA methylation; Epigenetic; MS-HRM; TET2.

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