# Microenvironment-induced metabolic plasticity in leukemia stem cells

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $355,706

## Abstract

The long-term objective of this proposal is to create more effective means by which to eradicate
leukemia stem cells (LSCs). While multiple strategies have been described in the literature,
finding approaches capable of broadly targeting LSC populations has remained elusive. We and
others have described extensive intra-patient heterogeneity in human LSC populations, which we
believe is an important factor to address in creating improved therapeutic regimens. To better
understand the cellular and molecular drivers of LSC heterogeneity, we have conducted studies
that demonstrate major differences in LSCs that occur purely as a function of their local tissue
microenvironment. Particularly striking are differences observed between LSCs in bone marrow
and adipose tissue, where upon localization to adipose tissue we observe a strong induction of
fatty acid oxidation (FAO), reduced cell cycle activity and increased resistance to chemotherapy
drugs. Thus, a central premise of the current application is that intra-patient LSC heterogeneity
can arise due to extrinsic (i.e. microenvironmental) factors that vary as a function of anatomical
site. Further, our data clearly imply a causal link between the microenvironment-induced
metabolic state of LSCs and their sensitivity to drugs.
The studies proposed herein are designed to identify and characterize key mechanisms that
control LSC metabolism as a function of microenvironment. Lines of investigation will include
analysis of cell intrinsic and extrinsic regulators of LSC metabolism.

## Key facts

- **NIH application ID:** 9830623
- **Project number:** 5R01CA220986-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Craig T. Jordan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,706
- **Award type:** 5
- **Project period:** 2017-12-06 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830623

## Citation

> US National Institutes of Health, RePORTER application 9830623, Microenvironment-induced metabolic plasticity in leukemia stem cells (5R01CA220986-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830623. Licensed CC0.

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