# Targeting of IL-1 Signaling in Myelofibrosis

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2024 · $215,179

## Abstract

Title: Targeting of IL-1 Signaling in Myelofibrosis
PROJECT SUMMARY/ABSTRACT
Myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET) and
myelofibrosis (MF) are a group of clonal hematopoietic stem cell derived myeloid malignancies characterized
by overproduction of myeloid lineage cells. MF is the deadliest among MPNs. The median survival of patients
with MF is ~5 years. The oncogenic JAK2V617F mutation was found in ~95% cases of PV and ~50-60% cases
of ET and MF. Mutations in the thrombopoietin receptor (MPL) and calreticulin (CALR) were also detected in
MF. Currently approved JAK inhibitors, Ruxolitinib and Fedratinib, can alleviate constitutional symptoms but
they do not offer significant improvement of bone marrow fibrosis. Therefore, there is an unmet need to identify
new therapeutic targets and develop novel therapies for MF. Chronic inflammation is frequently associated with
MPN/MF. Expression of interleukin-1 (IL-1), a master regulator of inflammation, is found elevated in MPN/MF
patients as well as in Jak2V617F knock-in mice. However, the contribution of IL-1 signaling in the
pathogenesis of MPN/MF has remained elusive. In preliminary studies, we have found that genetic deletion of
IL-1R1 normalizes peripheral blood counts, reduces splenomegaly and significantly inhibits bone marrow
fibrosis in a Jak2V617F knock-in mouse model of MF. So, we hypothesize that IL-1 signaling may play an
important role in the pathogenesis of MF and targeting of IL-1 signaling might be useful for treatment of MF. In
this proposal, we will further investigate the contribution of IL-1 signaling in the pathogenesis of MF and test
the efficacy of pharmacologic inhibition of IL-1 signaling in pre-clinical models of myelofibrosis. We will also
determine the mechanism by which inhibition of IL-1 signaling prevents the progression of MPN/MF. Results
from this study may lead to new therapeutic approach for treatment of myelofibrosis.

## Key facts

- **NIH application ID:** 10804665
- **Project number:** 5R21CA274430-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Golam Mohi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $215,179
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804665

## Citation

> US National Institutes of Health, RePORTER application 10804665, Targeting of IL-1 Signaling in Myelofibrosis (5R21CA274430-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10804665. Licensed CC0.

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