# Aberrant signaling in acute myeloid leukemia

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $481,665

## Abstract

Project Summary
Despite intense efforts, the long-term cure rates of children and adults with acute myeloid leukemia are not
satisfactory. Resistance to cytotoxic chemotherapy and apoptosis is the dominant cause of treatment failure.
The molecular mechanisms responsible for chemotherapy resistance are poorly understood, hindering the
development of therapeutic strategies to induce chemosensitivity. We have found that chemotherapy and
apoptosis resistance in high-risk AML requires aberrant phosphorylation of MEF2C, a key transcriptional
regulator of leukemia cell growth and survival. The central hypothesis of this proposal is that defining the
apoptotic mechanisms dysregulated by aberrant MEF2C signaling will reveal effective therapeutic strategies to
overcome treatment resistance. The applicant, who is a New Investigator, will test this hypothesis by
investigating the molecular mechanisms of apoptosis resistance in primary human and genetically-engineered
mouse leukemias. Aim 1 will elucidate both transcriptional and cellular mechanisms of therapy resistance, with
the goal of identifying MEF2C targets that are necessary and sufficient for chemoresistance. Aim 2 will pursue
the preliminary evidence that MARK family kinases aberrantly phosphorylate MEF2C and devise rational
combination strategies to overcome chemotherapy resistance induced by MEF2C phosphorylation. Successful
completion of this project is expected to yield molecular mechanisms of aberrant survival and chemotherapy
resistance of high-risk AML, thus providing essential insights into a fundamental biological and clinical problem,
which can be rapidly translated into clinical trials for patients with this disease.

## Key facts

- **NIH application ID:** 9984864
- **Project number:** 5R01CA204396-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Alex Kentsis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $481,665
- **Award type:** 5
- **Project period:** 2016-08-22 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984864

## Citation

> US National Institutes of Health, RePORTER application 9984864, Aberrant signaling in acute myeloid leukemia (5R01CA204396-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984864. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*