# Molecular targeting of erythroid progenitor cells in normal and disordered human erythropoiesis

> **NIH NIH R01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2021 · $475,637

## Abstract

Project Summary/Abstract
 Defects in erythropoiesis can ultimately lead to anemia, a major cause of morbidity and mortality
worldwide. Diamond Blackfan anemia (DBA), an inherited bone marrow failure syndrome, is an example of
disordered erythropoiesis and is currently only curable with hematopoietic stem cell transplantation.
 With the exception of cytokines, the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide
(Pom) and corticosteroids such as dexamethasone (Dex) are the primary pharmacologic agents that directly
improve red cell production in patients with erythropoietic defects. Nevertheless, the molecular basis for their
effects on erythroid progenitors and precursors is not fully understood. In addition, not all patients with DBA
respond to Dex, and only 40% of these have a sustained response without dose-limiting toxicity.
 The primary research focus of the present proposal is to develop comprehensive mechanistic
understanding of effects of Pom and GC on the erythroid progenitors, BFU-E and CFU-E, during human
erythropoiesis with the overarching goal to potentially combine them and treat the anemia seen in DBA and
other diseases to reduce GC dose-limiting toxicity in patients. Our preliminary data reveal that Pom
upregulates TEAD2 and silences the TGF-b at the BFU-E stage. In addition, Dex acts at the CFU-E stage in
models of human erythropoiesis. Finally, unlike CFU-E derived from and adult source of CD34+ cells, CFU-E
derived from cord blood are unresponsive to Dex.
 We hypothesize that silencing of TGF-b pathway by Pom will maximize the effects of Dex, thereby
limiting the dose needed to treat patients, and its toxicity. Here we propose to investigate the molecular
targeting of erythroid progenitors by Pom and Dex in human models of normal and disordered erythropoiesis
as proof of concept for the treatment of anemia. Specifically, we will (1) determine the mechanism of action of
Pom in human BFU-Es, (2) investigate the mechanism of action of Dex in human CFU-Es through the
dynamics of the glucocorticoid receptor and global regulation of the cell cycle, and (3) evaluate whether the
combination of Pom and Dex stimulates erythropoiesis in normal progenitor cells and progenitor cells from
patients with DBA.
 These studies will highlight the molecular mechanisms of action of Pom and Dex during human
erythropoiesis and further our understanding of normal and disordered red cell production and the appropriate
use of these drugs in improved clinical management of bone marrow failure syndromes. Given that these drugs
are already FDA-approved for a variety of hematological diseases, we further anticipate their combined use
may result in improved clinical managements of disorders with defective red cell production such as DBA.

## Key facts

- **NIH application ID:** 10084313
- **Project number:** 5R01HL144436-03
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Lionel Blanc
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $475,637
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084313

## Citation

> US National Institutes of Health, RePORTER application 10084313, Molecular targeting of erythroid progenitor cells in normal and disordered human erythropoiesis (5R01HL144436-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10084313. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*