# Dependency of AML on CARM1 activity

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $370,596

## Abstract

Project Summary/ Abstract
Defining the genetic and epigenetic abnormalities that drive cellular transformation has provided
insights into potential therapeutic approaches to cancer. However, the myriad of genetic changes
that accompany specific types of cancer makes it difficult to find therapeutic approaches
applicable to the bulk of patients with a given disease. We have identified an oncogenic role for
the epigenetic enzyme “co-activator associated arginine methyltransferase 1” (CARM1) in AML,
and a dependency of AML cells, but not normal hematopoietic stem cells, on CARM1 activity.
CARM1 methylates a variety of histone and non-histone substrates and targeting its activity, via
small molecule inhibitors, knockdown (KD) or knockout (KO) approaches, triggers AML cell
differentiation and death. The proposed studies represent a conceptual shift from targeting
specific mutations found in AML to developing therapies that target chromatin modifiers and
transcriptional regulators that are essential to large numbers of AML patients. To advance this
new paradigm we have proposed the following specific aims:
Aim 1: We will define the molecular basis for the differentiation-promoting effects of CARM1
inhibition on AML cells, identifying the critical CARM1-interacting proteins, substrates and
target genes that regulate myeloid differentiation, proliferation and survival. We will use state-of-
the-art techniques including the BioID2 system, mass-spectrometry, RNA-Seq and
ChIP-Seq. Aim 2: We will determine the mechanisms that control the level of CARM1
activity in AML cells, defining how changes in CARM1 mRNA levels, protein levels, and post-
transcriptional modifications, including phosphorylation, affect CARM1 activity in AML cells. Aim
3: Determine the basis for the unique sensitivity of AML cells to CARM1 inhibition or KD. We will
also define CARM1 inhibitor resistance mechanisms, and test CARM1 inhibitor-containing
combination therapies, using human AML cell lines and primary AML samples and NOD/SCID
mice engrafted with human AML cells. These studies will help establish the importance of CARM1
in the pathogenesis of AML, and advance our understanding of how CARM1 inhibitors can be
used as part of an effective and novel “epigenetic-targeted” strategy for treating cancer.

## Key facts

- **NIH application ID:** 10912450
- **Project number:** 5R01CA251664-05
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Stephen D. Nimer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $370,596
- **Award type:** 5
- **Project period:** 2020-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912450

## Citation

> US National Institutes of Health, RePORTER application 10912450, Dependency of AML on CARM1 activity (5R01CA251664-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10912450. Licensed CC0.

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