# Molecular Mechanism of Leukemogenesis involving AML1-ETO

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $367,745

## Abstract

R01 CA104509-15 “Molecular Mechanism of Leukemogenesis involving AML1-ETO”
PROJECT SUMMARY
Cancer is the most devastating human disease in the world, affecting almost everyone directly or indirectly.
Acute myeloid leukemia (AML) is a highly heterogeneous and aggressive hematological cancer. One of the
most common genetic abnormalities in AML is the t(8;21) chromosomal translocation, resulting in the fusion
transcription factor AML1-ETO. Due to currently unclear reasons, t(8;21) AML patients are younger and
respond to initial induction chemotherapy better than most other AML patients. However, only 50-60% of
t(8;21) AML patients respond to initial chemotherapy and ~40% of initial responders relapse. Further treatment
options after relapse are limited and prognosis is generally poor. Therefore, we still need to understand the
unique molecular basis of t(8;21) AML to expand therapeutic options for treating and saving these patients.
Our long-term goal is to identify critical molecular pathogenic events that promote development and
maintenance of AML as potential therapeutic targets. The overall objectives of this competitive renewal
application are to elucidate the critical chromatin remodeling events that promote t(8;21) AML and to
characterize vulnerabilities of t(8;21) AML that will facilitate elimination of leukemia cells. Our central
hypothesis is that molecular alterations directly caused by expression of AML1-ETO provide unique
pathological conditions of t(8;21) AML, which can be targeted by novel therapies. To attain the overall
objectives, the following two specific aims will be pursued: 1) Analyze the combinatory effect of t(8;21) and KIT
mutations on leukemogenesis through integrative transcriptome and epigenome studies in mouse models and
2) Characterize glutathione and oxidative phosphorylation in sensitizing t(8;21) AML to cell death. Together,
these proposed studies are based on our accumulated knowledge, our most recent findings, and the potential
therapeutic impact of the work. Collectively, this proposal will address important unanswered questions in
t(8;21) AML and provide valuable insights into the molecular pathology of human leukemia.

## Key facts

- **NIH application ID:** 10374149
- **Project number:** 5R01CA104509-17
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** DONG-ER ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,745
- **Award type:** 5
- **Project period:** 2004-07-16 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374149

## Citation

> US National Institutes of Health, RePORTER application 10374149, Molecular Mechanism of Leukemogenesis involving AML1-ETO (5R01CA104509-17). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10374149. Licensed CC0.

---

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