# Clinical and Genetic Origins of Monomorphic Epitheliotropic Intestinal T Cell Lymphoma

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $395,772

## Abstract

ABSTRACT
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare but lethal disease with a median
survival of 1 year. There is no current effective standard-of-care. Previous MEITL sequencing efforts performed
by our group and others have revealed SETD2 as one of the most frequently altered genes in this disease.
SETD2 directs trimethylation of the lysine 36 residue on histone H3 (H3K36me3), which in turn is associated
with active transcription of genes. SETD2 has been implicated in DNA damage repair and mRNA splicing.
However, the molecular role of SETD2 and its interaction with activated oncogenes in MEITL pathogenesis is
largely unknown.
In this proposal, we will utilize a conditional mouse model to determine how SETD2 loss contributes to the
creation of a premalignant pool of intestinal intraepithelial cells (IELs), the cell of origin of MEITL. We will also
investigate how the combination of SETD2 loss and activation of the oncogenes STAT5B or MYC lead to IEL
transformation. Finally, we will determine the extent to which SETD2 deficiency sensitizes T lymphoma cells to
a variety of genotoxic chemotherapeutics. We anticipate that the results of this work will have immediate impact
on the design of effective treatment regimens that target MEITL and other SETD2-deficient lymphomas.

## Key facts

- **NIH application ID:** 10758565
- **Project number:** 5R01CA277192-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sandeep Dave
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $395,772
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758565

## Citation

> US National Institutes of Health, RePORTER application 10758565, Clinical and Genetic Origins of Monomorphic Epitheliotropic Intestinal T Cell Lymphoma (5R01CA277192-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10758565. Licensed CC0.

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