Loss of TET2 with reduced genomic 5-hmC is associated with adverse-risk AML

Abstract

While considerable information exists on the ten-eleven translocation 2 (TET2) mutational landscape in AML, the information on TET2 expression is limiting. So, we aimed to study the TET2 expression at mRNA and protein levels in AML patients compared to healthy controls. To achieve this, we recruited 70 non-M3, de novo AML patients and 20 healthy controls. The expression of TET2 was checked at mRNA and protein levels by qPCR and ELISA respectively and the TET activity was checked by the 5-hmC assay. TET2 mRNA expression was correlated with clinicopathological parameters and overall survival. We found a significant downregulation of TET2 mRNA and protein and significantly lower DNA 5-hmC levels in AML patients compared to controls. TET2 downregulation was more in patients with high blast counts and patients of the adverse-risk ELN category. We also found a significant upregulation of DNMT1 and DNMT3a suggesting a hypermethylation phenotype in de novo AML.

Keywords:

• Acute myeloid leukemia
• TET2
• DNMT
• cancer epigenetics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Indian Council of Medical Research under the research associate fellowship to the first author and Science and Engineering Research Board under Early Career Research grant to the corresponding author [ECR/2015/000236].