# Adipose Tissue Reprograms Acute Lymphoblastic Leukemia Cells to Facilitate CNS and Bone Invasion

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $236,073

## Abstract

PROJECT SUMMARY
Obesity is associated with an increased risk of relapse from acute lymphoblastic leukemia (ALL), the most
common childhood cancer. We have uncovered a novel mechanism by which fat tissue may make ALL more
aggressive and harder to cure. ALL cells found in adipose tissue in mouse models have a higher expression of
RANKL (receptor activator of nuclear factor kappa-B ligand) than ALL found in marrow. Exposing ALL cells to
adipose tissue ex vivo also increases their expression of RANKL. RANKL is known to contribute to ALL cell
expansion in vivo, as well as invasion into bone and the central nervous system (CNS). In the present grant, we
will investigate the pathways by which adipose tissue increases ALL expression of RANKL. We will explore this
finding using a translational approach, with experiments ranging from bench to mouse to evaluations of clinical
samples. We will elucidate which adipose tissue-derived signals are responsible for ALL cell RANKL expression.
We will examine whether obesity increases ALL RANKL expression in mice and clinical samples, and explore
the relationships between RANKL expression and bone density, CNS invasion, and chemotherapy treatment
response. Finally, we will test an FDA-approved treatment, denosumab, in mice to see whether impairing RANKL
signaling can improve ALL treatment outcome. These studies may provide a novel strategy for ALL patients to
reduce bone loss and fractures, reduce CNS invasion, and potentially improve chemotherapy treatment
outcomes.

## Key facts

- **NIH application ID:** 10866264
- **Project number:** 1R21CA289085-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Steven David Mittelman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $236,073
- **Award type:** 1
- **Project period:** 2024-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866264

## Citation

> US National Institutes of Health, RePORTER application 10866264, Adipose Tissue Reprograms Acute Lymphoblastic Leukemia Cells to Facilitate CNS and Bone Invasion (1R21CA289085-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10866264. Licensed CC0.

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