Understanding how CMML develops and becomes aggressive
Molecular and Cellular Mechanisms of Chronic Myelomonocytic Leukemia (CMML)
['FUNDING_R01'] · UNIVERSITY OF WISCONSIN-MADISON · NIH-11306692
Looks at blocking overactive MEK/ERK signals and BET protein-driven gene activity to slow or reverse aggressive CMML and lower its chance of turning into AML for people whose leukemia has NRAS and ASXL1 mutations.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF WISCONSIN-MADISON (nih funded) |
| Locations | 1 site (MADISON, UNITED STATES) |
| Trial ID | NIH-11306692 on ClinicalTrials.gov |
What this research studies
This work uses blood and clinical data from people with CMML alongside specially engineered mice that carry the same NRAS and ASXL1 changes seen in some patients. Researchers study how overactive MEK/ERK signaling and BET protein-related gene activity drive disease progression and immune suppression. They focus on AP-1 transcription factors and immune checkpoint signals (like PD-L1 and CD86) that make the leukemia environment less responsive to immune attack. In mice, combining drugs that block MEK and BET proteins reduced those signals and improved CD8 T cell activity, suggesting a possible path toward new treatments.
Who could benefit from this research
Good fit: People with a diagnosis of CMML, especially those whose leukemia carries NRAS and ASXL1 mutations or who are at high risk of progression to AML.
Not a fit: Patients without NRAS and ASXL1 mutations or those with other unrelated blood cancers are less likely to benefit from the specific approaches studied here.
Why it matters
Potential benefit: Could lead to new combination therapies that slow CMML progression and reduce transformation to AML for patients with NRAS and ASXL1 mutations.
How similar studies have performed: Preclinical studies, including the investigators' mouse models, have shown promise for combined MEK and BET inhibition, but patient benefit has not yet been proven in clinical trials.
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.