# Developing Acute Myeloid Leukemia Models with Diverse Ancestral Origins

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $213,594

## Abstract

Project Summary
Acute myeloid leukemia (AML) is an aggressive cancer of the bone marrow. There is a well-documented
survival disparity with non-Hispanic white (NHW) patients having a better outcome compared to non-Hispanic
black (NHB) patients. To date, clinical trials with minimal NHB patient participation are the basis for all
approved treatments and risk stratification systems. How ancestral racial backgrounds are reflected in AML
that arises in NHB patients is largely unknown. This may have led to treatment practices that are not optimal
for NHB patients. Indeed, in contrast to NHWs who have a good prognosis, NHB patients with NPM1 mutations
have an adverse prognosis when treated with standard therapies. The lack of preclinical models of NHB origins
further exacerbate this lack of knowledge. As a result, there is little to no preclinical or clinical evidence to what
extent the current approved therapies in AML are efficacious in NHB patients. This is clearly unacceptable.
This proposal seeks to leverage novel approaches to generate preclinical AML models of NHB origins and to
compare therapy responses and basic biochemical properties to models generated from NHW patients. This
will be accomplished in the 3 aims of this proposal. They are 1) Utilize the Sleeping Beauty (SB) transposon
system to generate AML models from CD34+ cells derived from healthy donors of NHB and NHW origins; 2)
Characterize racial differences in therapy sensitivity and DNA damage response in AML models; 3) Develop
patient derived organoid models from NHW and NHB AML patients; The results from this study will greatly
inform the influence of racial ancestry on AML arising from NHB patients. This information will guide new
strategies geared specifically towards AML in NHB patients and will inform drug development efforts to ensure
future therapies are efficacious for AML patients of all racial backgrounds.

## Key facts

- **NIH application ID:** 10889695
- **Project number:** 1R21CA283135-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Timothy Sebastian Pardee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $213,594
- **Award type:** 1
- **Project period:** 2024-03-18 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889695

## Citation

> US National Institutes of Health, RePORTER application 10889695, Developing Acute Myeloid Leukemia Models with Diverse Ancestral Origins (1R21CA283135-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10889695. Licensed CC0.

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