How ASXL1 mutations change aging blood stem cells
Molecular and Cellular Mechanisms of Mutant ASXL1-driven Clonal Hematopoiesis
Researchers are looking at how a common ASXL1 gene mutation causes age-related changes in blood stem cells and whether targeting cell-survival pathways can reduce harmful cell expansion.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Wisconsin-Madison NIH-funded |
| Lab location | 1 site (Madison, United States) |
| Project ID | NIH-11180108 on NIH RePORTER |
What this research studies
From a patient's view, this work studies a common age-related condition called clonal hematopoiesis (CHIP) driven by ASXL1 mutations that can raise the risk of blood cancers. The team uses mouse models carrying the ASXL1 hotspot mutation and compares young versus old bone marrow environments to see how inflammation, senescent stromal and endothelial cells, and epigenetic changes help mutant stem cells expand. They test whether blocking anti-apoptotic proteins (for example with the drug ABT-263) can reduce survival of senescent niche cells and alter mutant cell growth. Findings could point to ways to interrupt the unhealthy bone marrow environment that helps pre-leukemic clones grow.
Who could benefit from this research
Good fit: People most relevant to this research are older adults with clonal hematopoiesis, especially those known to carry ASXL1 mutations or unexplained age-related changes in blood counts.
Not a fit: Young healthy people without CHIP or patients whose blood conditions are unrelated to ASXL1 mutations are unlikely to get direct benefit from this specific work.
Why it matters
Potential benefit: If successful, this work could lead to new ways to prevent or slow progression of ASXL1-driven clonal hematopoiesis and reduce future blood cancer risk by targeting survival pathways in the bone marrow niche.
How similar studies have performed: Related lab and animal studies have shown that BCL-2/BCL-XL inhibitors can clear senescent cells, but applying these approaches specifically to ASXL1-driven CHIP is a newer direction.
Where this research is happening
Madison, United States
- University of Wisconsin-Madison — Madison, United States (Active)
Researchers
- Principal investigator: Zhang, Jing — University of Wisconsin-Madison
- Study coordinator: Zhang, Jing
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.