# Impact of chronic intermittent hypoxia on the bone marrow

> **NIH NIH R56** · UNIVERSITY OF IOWA · 2020 · $384,838

## Abstract

PROJECT ABSTRACT
Sleep apnea is an underdiagnosed condition strongly associated with obesity, and linked to increased cancer
mortality. Multiple myeloma is an incurable cancer of antibody-secreting bone marrow plasma cells associated
with obesity, whose etiology is poorly understood. We found a previously unrecognized link between chronic
intermittent hypoxia, a cardinal feature of sleep apnea, and myeloma in both patients and in a mouse model of
myeloma. We found that 51% of myeloma clinic patients are at high risk of sleep apnea by questionnaire, and
that sleep apnea risk was associated with a 10-fold increase in the serum free light ratio, a marker of disease
burden. In our first 12 myeloma patients enrolled on a prospective nighttime oximetry trial, we found 11
patients (92%) to have evidence of nighttime hypoxia consistent with sleep apnea (20-fold increased risk
compared to age-matched historical controls). In mice, we found that chronic intermittent hypoxia (CIH)
stimulated myeloma cell bone marrow engraftment and lethal disease. CIH also caused gene expression
changes in the bone marrow significantly associated with angiogenesis and B-cell development pathways.
Here, we propose mechanistic studies in mice to test the hypothesis that CIH causes bone marrow
microenvironment changes that support mutant plasma cell accumulation and disease progression: Aim 1:
Test the hypothesis that intermittent hypoxia promotes the pathogenic expansion of mutated plasma cells in
the bone marrow in additional models of myeloma; Aim 2: Map the anatomic changes to the bone marrow
vasculature and macrophage populations, and effects on plasma cell distribution induced by intermittent
hypoxia; Aim 3: Interrogate the mechanistic contributions of sympathetic-mediated signaling on bone marrow
remodeling and lethal engraftment of myeloma cells. Together, these studies will elucidate the mechanisms by
which CIH contributes to myeloma pathogenesis and will provide the foundation for clinical trials testing the
role CIH in myeloma development and response to therapy.

## Key facts

- **NIH application ID:** 10241766
- **Project number:** 1R56HL152365-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Melissa Lowe Bates
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,838
- **Award type:** 1
- **Project period:** 2020-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241766

## Citation

> US National Institutes of Health, RePORTER application 10241766, Impact of chronic intermittent hypoxia on the bone marrow (1R56HL152365-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241766. Licensed CC0.

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