# Exploring the link between serine metabolism and epigenetic in lymphoma

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $569,395

## Abstract

Exploring the link between serine metabolism and epigenetics in lymphoma
Project description
Follicular lymphoma (FL) is the second most common form of lymphoma and remains incurable despite
advances against other forms of lymphoma. We noticed that ~30% of FL (and also DLBCLs) carry an
amplification of the SHMT2 gene that encodes the enzyme serine hydroxymethyltransferase-2 - a key enzyme
in serine metabolism. SHMT2 converts serine to glycine and this reaction yields activated methyl groups for
biosynthetic and modification reactions including DNA and histone methylation. Serine metabolism has been
implicated in cancer, for example PGHDH is amplified in breast cancer (Possemato et al. 2011, Beguelin et al.
2017), and SHMT2 levels correlate with proliferation across cancer cell lines (Ye et al. 2014). Lymphoma is, in
large part, an epigenetic disease and we have characterized the most frequent causative mutations that affect
epigenetic drivers such as KMT2D/MLL2, CREBBP/EP300, EZH2 and others (Kridel et al. 2012, Ortega-Molina
et al. 2015, Jiang et al. 2017, Zhang et al. 2017).
We speculate that aberrant serine catabolism is a driver of
lymphoma biology and produces activated methyl groups that alter the epigenetic state of lymphoma cells. Our
preliminary data support this new link between metabolism and epigenetics in lymphoma
. For example, i) we
find that SHMT2 acts as a driver of lymphoma development in a mouse model, ii) Metabolomics studies show
increased production of S-adenosyl methionine (the donor of activated methyl groups) in SHMT2 driven
lymphomas, and iii) human and murine SHMT2 amplified lymphomas show characteristic changes in DNA and
histone methylation and gene expression. Based on these data we speculate that serine catabolism drives
epigenetic modification and this contributes to lymphoma development in vivo. Moreover, aggressive lymphomas
and cell lines depend on SHMT2 for growth and this requirement signals a potential therapeutic opportunity that
we need to explore. In this project, we will explore the link between serine catabolism and epigenetics in a deadly
form of lymphoma and we will test the potential for therapeutic intervention.
!

## Key facts

- **NIH application ID:** 9943206
- **Project number:** 1R01CA248168-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Hans-Guido Wendel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $569,395
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9943206

## Citation

> US National Institutes of Health, RePORTER application 9943206, Exploring the link between serine metabolism and epigenetic in lymphoma (1R01CA248168-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9943206. Licensed CC0.

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