Targeting the stem cells that drive myelofibrosis
Official title: Project 3: Development of Strategies to Deplete Myelofibrosis Stem Cells
Funded at Icahn School of Medicine at Mount Sinai · NIH-11094805 · Data updated 2026-11-12
Using drugs that boost the tumor-suppressor p53 to help remove the abnormal bone marrow stem cells that cause myelofibrosis in people with the disease.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project start | July 1, 2006 |
| Project end | May 31, 2028 |
| Funding year | 2025 |
| Award (this year) | $462,546 |
| NIH project number | 5P01CA108671-17 |
| Project ID | NIH-11094805 on NIH RePORTER |
Who could benefit from this research
✓Could help
People diagnosed with myelofibrosis who are medically eligible for investigational HDM2-targeting therapy and can attend trial visits.
✕Less likely to help
People without myelofibrosis, those whose disease carries TP53 (p53) mutations that inactivate p53, or those already in blast-phase disease may not benefit from this approach.
What this research studies
This work focuses on medicines that block HDM2, a protein that destroys p53, so p53 can rise and prompt the abnormal myelofibrosis stem cells to die. Early lab and clinical work with an HDM2 blocker (nutlin) showed these drugs can lower disease-driving mutation levels, improve symptoms, and reverse bone marrow fibrosis while sparing normal stem cells. The project is developing and testing strategies to selectively deplete myelofibrosis stem/progenitor cells and to reduce harmful inflammation driven by NFκB. From a patient's perspective, this aims to treat the root cells that keep the disease going rather than only easing symptoms.
Why it matters
Potential benefit: If successful, this could lower the number of disease-causing stem cells, reduce mutation burden and marrow fibrosis, improve symptoms, and decrease the risk of progression to blast phase.
How similar studies have gone: Early clinical trials of HDM2 antagonists such as nutlin have reported clinical improvements, reductions in driver mutation levels, and reversal of fibrosis, providing promising preliminary evidence.
Where this research is happening
-
Icahn School of Medicine at Mount Sinai
New York, United States Active
Researchers
- Principal investigator: Hoffman, Ronald — Icahn School of Medicine at Mount Sinai
- Study coordinator: Hoffman, Ronald
Related research
Other NIH-funded projects on the same topics.
-
Strategies to deplete myelofibrosis stem cells using HDM2/p53 pathway
A patient-focused program tests a therapy that may selectively reduce disease-causing blood stem cells in people with myelofibrosis.
-
Megakaryocyte changes in myelofibrosis and its progression to leukemia
A scientist-guided project will study how abnormal megakaryocytes and signals like TGF-β and IL-13 may drive progression from myelofibrosis toward acute leukemia, with potential implications for future treatments.
-
Molecular clues and new therapies for myelofibrosis and related blood cancers
This grant supports research to understand what drives myelofibrosis and related disorders and to develop new treatment ideas for patients.
-
Myelofibrosis and the bone marrow environment: how inflammation changes blood production
A doctor-researcher is studying how inflammation in the bone marrow affects the blood-forming system in people with myeloproliferative neoplasms (MPNs) to find ways to prevent scarring and leukemia.
-
Early detection of treatment response in myelofibrosis using a new imaging technology
A new, quick imaging method could tell patients with myelofibrosis early whether a treatment is working.
-
MYC-driven vulnerability in myelofibrosis could guide new therapies
A new project is exploring how the MYC protein contributes to myelofibrosis and whether it can be targeted to help people with this blood cancer.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.