# Role of DDX41 in HSC development and MDS/AML

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $239,850

## Abstract

Dead-box helicase 41 (DDX41) is a known sensor of nucleic acids that contributes to the
interferon response to retroviruses. DDX41 belongs to a family of RNA helicases, with distinct
DEAD/H box (Asp-Glu-Ala-Asp/His) domains, whose members have been implicated in
translation, ribosome biogenesis, nuclear-cytoplasmic transport, organelle gene expression and
pre-mRNA splicing. DDX41 was also recently identified as a tumor suppressor gene in familial
and sporadic myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), as well as other
hematological malignancies. In MDS/AML, DDX41 is thought to interact with spliceosomal
components and alter splicing, resulting in the inactivation of tumor suppressor genes or
alterations in the balance of gene isoforms, although whether this occurs through protein-RNA,
protein-DNA or protein-protein interactions is not known. We recently developed mice with a
floxed allele of DDX41, which will allow us for the first time to study DDX41's role in hematopoietic
development and transformation. DDX41 germline knockouts die prior to E10 in development, but
mice heterozygous for the knockout are completely viable and will be used to determine whether
these mice develop myelodysplasias. We have also generated conditional knockouts that delete
the gene in hematopoietic stem cells (HSC). The HSCs will be used to study the role of DDX41
in hematopoietic lineage differentiation. RNA Seq analysis on the knockout HSCs will be
performed, to determine if loss of DDX41 results in altered gene expression or splicing defects.
The HSCs will be transduced with wild type and mutant DDX41; in particular, we will engineer
patient-derived mutations as well those in the DEAD and helicase domains, to begin to determine
how this protein functions in development and transformation. We propose to use these mice to
study the role of DDX41 in HSC development, as well as to determine the mechanism by which
it regulates transformation of myeloid cells. These studies are likely to further our understanding
of AML as well as to generate a model system for testing potential therapeutics.

## Key facts

- **NIH application ID:** 10216402
- **Project number:** 1R21AI153594-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** SUSAN R ROSS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $239,850
- **Award type:** 1
- **Project period:** 2021-03-16 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216402

## Citation

> US National Institutes of Health, RePORTER application 10216402, Role of DDX41 in HSC development and MDS/AML (1R21AI153594-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10216402. Licensed CC0.

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