# RETINOIDS IN HEMATOPOIESIS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,250

## Abstract

Abstract
Retinoid receptors are transcription factors that play important roles regulating self-renewal and maturation of
bone marrow cells, and can be changed from transcriptionally inactive states, to transcriptionally active states,
by the presence of a retinoid ligand. The distribution and regulation of natural retinoid ligands is unknown.
There are only two FDA approved applications for retinoid therapy in hematology (all-trans retinoic acid for
acute promyelocytic leukemia, and bexarotene for cutaneous T cell lymphoma). Other attempts to integrate
retinoid-based therapy into clinical hematology have been done through empiric testing, and have not been
informed by a rational understanding of retinoid biology in bone marrow cells. We have developed a novel in
vivo retinoid reporter assay, to determine which bone marrow cells are exposed to natural retinoids, and
whether these are regulated by physiologic or pathologic stress. Unexpectedly, we have found that RXRA, but
not RARA or RARG, natural retinoids are present in mouse bone marrow cells, and that these exist
intracellularly in myeloid and erythroid progenitor cells, but not in stem cells. In this study, we will further define
the distribution and regulation of natural retinoids in bone marrow cells in response to physiologic
hematopoietic stressors (e.g. response to cytokines or recovery from cytopenias). We will determine, in which
cells natural retinoids are present, and when. We will further determine whether retinoids exist intracellularly
following pathologic stress (e.g. leukemia). We will determine whether natural retinoids exists in mature
leukemias (monocytic and erythroleukemias) vs immature leukemias, whether this might render these forms of
AML sensitive to retinoid agonists vs antagonists, and whether response could be augmented in specific forms
of leukemia by inhibition of intracellular or niche-based retinoid elimination. Finally, we will identify what these
natural RXR ligands are. These studies will illuminate the mechanism of retinoid sensitivity vs resistance in
bone marrow cells, and will help guide the integration of retinoid therapy into clinical hematology.

## Key facts

- **NIH application ID:** 9847994
- **Project number:** 5R01HL128447-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JOHN S WELCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2016-02-10 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9847994

## Citation

> US National Institutes of Health, RePORTER application 9847994, RETINOIDS IN HEMATOPOIESIS (5R01HL128447-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9847994. Licensed CC0.

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