# TET-mediated Epigenetic Regulation in the Development and Immunoevasion of B cell Lymphoma

> **NIH NIH K22** · OHIO STATE UNIVERSITY · 2021 · $161,751

## Abstract

Abstract
Dysregulated epigenome has emerged as the hallmark of cancers. For instance, more than 80% of diffuse
large B cell lymphoma (DLBCL) carries the mutation in at least one epigenetic regulator, including TET2. TET
proteins (Ten-Eleven Translocation; TET1, TET2, TET3) are dioxygenases that oxidize the methyl group of 5-
methylcytosine (5mC) primarily to 5-hydroxymethylcytosine (5hmC), a stable epigenetic mark and an essential
intermediate for DNA demethylation. Despite TET mutation strongly associates with cancers, the mechanism
by which TET proteins suppress cell transformation is not well understood. Mutation of Tet resulted in
dysregulated B cell proliferation. Unexpectedly, TET-mutation in B cells affects T cells in trans and creates a
microenvironment permissive to cell transformation. In this K22 proposal, I will extend these studies to
investigate the role of TET enzymes in regulating the epigenome of GC B cells and their malignant
transformation into DLBCL. Specifically, I will test the hypothesis that TET proteins prevent B
lymphomagenesis by cell-intrinsically regulating the epigenome of B cells and extrinsically affecting
the bystander T cells. To address this hypothesis, I propose the following Specific Aims. In Aim 1, I will
profile the hydroxymethylome and define the TetEs normal and transformed germinal center B cells from
mouse and human. In Aim2, I will investigate the functional collaboration between TET and other epigenetic
regulators. I will also use a novel proteomics approach to analyze locus-specific proteomics at TetEs. In Aim 3,
I will examine unexpected crosstalk between Tet-deficient B cells and T cells. This K22 proposal will allow me
to acquire the necessary skills to be an independent investigator. Completion of this proposal will provide
significant insight into the molecular mechanism in the link between epigenome dysregulation and B cell
transformation. Finally, the results will likely lead to the therapeutic strategies for cancer by targeting the
epigenetic machinery and/or by modulating the anti-cancer immune response.

## Key facts

- **NIH application ID:** 10242616
- **Project number:** 5K22CA241290-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jerry Chan-Wang Lio
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,751
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242616

## Citation

> US National Institutes of Health, RePORTER application 10242616, TET-mediated Epigenetic Regulation in the Development and Immunoevasion of B cell Lymphoma (5K22CA241290-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242616. Licensed CC0.

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