Targeting the stem cells that drive myelofibrosis
Project 3: Development of Strategies to Deplete Myelofibrosis Stem Cells
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 ID | NIH-11094805 on NIH RePORTER |
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.
Who could benefit from this research
Good fit: People diagnosed with myelofibrosis who are medically eligible for investigational HDM2-targeting therapy and can attend trial visits.
Not a fit: 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.
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 performed: 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
New York, United States
- 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
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 below.