# Role of ASXL1 in normal and abnormal granulopoiesis.

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $479,787

## Abstract

PROJECT SUMMARY
ASXL1 is an epigenetic regulatory protein that is frequently mutated in myelodysplastic
syndromes and myeloproliferative neoplasms. Mutations in ASXL1 are associated with
treatment resistance and poor prognosis. ASXL1 mutations are highly enriched in CSF3R-
mutant myeloproliferative neoplasms, disorders characterized by an increased production of
neutrophils. Despite the high frequency of ASXL1 mutations and association with poor
prognosis, there is little known about the function of ASXL1 in normal or abnormal neutrophil
production. Through single cell RNA sequencing, we identified an essential role for ASXL1 in
normal neutrophil development. In this context, deletion of ASXL1 perturbs RNA polymerase II
function and activates a Myc signaling network in the neutrophil progenitor population. The goal
of this proposal is to define the molecular mechanisms by which ASXL1 controls the neutrophil
developmental program, and to understand how truncating mutations in ASXL1 contribute to the
biology of myeloproliferative disorders. Our long-term objective is to use this mechanistic
understanding to develop therapeutic interventions that reverse the defects in neutrophil
development associated with ASXL1 mutations.

## Key facts

- **NIH application ID:** 10180659
- **Project number:** 1R01HL157147-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Julia E Maxson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,787
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180659

## Citation

> US National Institutes of Health, RePORTER application 10180659, Role of ASXL1 in normal and abnormal granulopoiesis. (1R01HL157147-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10180659. Licensed CC0.

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