# Understanding and targeting bone marrow microenvironment in myelofibrosis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $563,550

## Abstract

Project summary/Abstract
Understanding and targeting abnormal tumor microenvironment is critically important for developing effective
therapy. Primary myelofibrosis (PMF) is a form of myeloproliferavtie neoplasm (MPN) that often progresses to
lethal leukemia. Treatment options are limited for PMF, and the only potential cure, stem cell transplantation, is
prohibitively toxic for most patients. Thus, novel and effective therapies are in great need for PMF. Recurrent
mutations resulting in abnormal activation of the JAK-STAT pathway have been shown to be the driver of the
disease. As a result, JAK inhibitors have been developed to treat PMF. However, these inhibitors only reduce
some constitutional symptoms without significant impact on disease-causing leukemia stem cells (LSCs). A
deeper understanding of the pathogenesis of PMF will offer the opportunity to better treat the disease. The
bone marrow niche is a critical component to the pathogenesis of PMF. Our preliminary data show that bone
marrow LepR+ stromal cells are the source of fibrosis. We have also identified several key mediators of LepR+
cell fibrosis. In this proposal, we propose to elucidating the cellular and molecular mechanisms of how LSCs
interact with the fibrotic niche in vivo. We will test whether targeting the fibrosis mediators will lead to efficient
elimination of LSCs and have synergistic effects with JAK inhibitors. By having a deeper understanding of the
interaction between LSCs and the niche, our strategy of targeting the diseased niche may provide novel
therapeutics to PMF.

## Key facts

- **NIH application ID:** 10755697
- **Project number:** 5R01HL155868-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Lei Ding
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $563,550
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10755697

## Citation

> US National Institutes of Health, RePORTER application 10755697, Understanding and targeting bone marrow microenvironment in myelofibrosis (5R01HL155868-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10755697. Licensed CC0.

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