# Novel molecular agents targeting NF-κB c-Rel O-GlcNAcylation for the treatment of acute myeloid leukemia.

> **NIH NIH R21** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $232,677

## Abstract

Abstract
Acute Myeloid Leukemia (AML) is the most prevalent form of acute leukemia with an
overall poor prognosis. Cancer cells including AML cells consume high glucose and
show altered glucose metabolism, which increases glycosylation of intracellular proteins
in a process called O-GlcNAcylation. We discovered that O-GlcNAcylation of several
proteins is significantly increased in AML cells and inhibition of global O-GlcNAcylation
leads to the death of AML cells. We also found that the transcription factor nuclear factor
kappaB (NF-κB) c-Rel is mono-O-GlcNAcylated at serine residue 350 in AML cells. c-Rel
controls the expression of several genes involved in AML cell survival and disease
progression. We have developed a novel peptoid, a peptidomimetic agent called
peptoid3, for specific targeting of O-GlcNAcylated c-Rel function. Our preliminary studies
using AML cell lines show that the peptoid3 treatment significantly decreased the
expression of multiple c-Rel-dependent genes involved in AML survival and caused
death of AML cells. This is a unique and novel approach that specifically kills AML cells
sparing normal white blood cells. This study will explore the ability of the novel agent,
peptoid3, to control AML progression using primary AML cells from patients of various
subtypes such as M1-M5 as well as using xenograft mouse models. Successful
completion of this preclinical study will reveal O-GlcNAcylated c-Rel as a key player
controlling AML cell growth and a potential therapeutic target. This study with future
translational work has the potential to yield an oral therapeutic, which may significantly
reduce the healthcare cost and improve the lives of patients suffering from AML.

## Key facts

- **NIH application ID:** 10111490
- **Project number:** 5R21CA246194-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Reshmi Parameswaran
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $232,677
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111490

## Citation

> US National Institutes of Health, RePORTER application 10111490, Novel molecular agents targeting NF-κB c-Rel O-GlcNAcylation for the treatment of acute myeloid leukemia. (5R21CA246194-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10111490. Licensed CC0.

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