Understanding how CMML develops and becomes aggressive
Official title: Molecular and Cellular Mechanisms of Chronic Myelomonocytic Leukemia (CMML)
Funded at University of Wisconsin-Madison · NIH-11306692 · Data updated 2026-11-12
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
| 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 start | September 2, 2011 |
| Project end | March 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $406,245 |
| NIH project number | 5R01CA152108-14 |
| Project ID | NIH-11306692 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
Patients without NRAS and ASXL1 mutations or those with other unrelated blood cancers are less likely to benefit from the specific approaches studied here.
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.
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 gone: 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
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University of Wisconsin-Madison
Madison, United States Active
Researchers
- Principal investigator: Zhang, Jing — University of Wisconsin-Madison
- Study coordinator: Zhang, Jing
Related research
Other NIH-funded projects on the same topics.
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Targeted therapies for a blood cancer called CMML (CBL-mutant CMML)
A physician-scientist is testing targeted drugs to treat a hard-to-kill blood cancer called CMML in patients whose cancer has CBL mutations.
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Blocking PLK1 in RAS‑mutated chronic myelomonocytic leukemia
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How inflammation changes blood stem cells and drives progression in chronic myelomonocytic leukemia
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Researchers are using mice implanted with patients' CMML cells to try out new treatment approaches for people with chronic myelomonocytic leukemia.
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This study is looking at how some people with chronic myelomonocytic leukemia (CMML) might not respond to a treatment called cobimetinib, and it aims to help those patients by figuring out why that happens and finding better ways to treat them.
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Targeting a specific protein to treat a type of blood cancer
This study is looking at a new pill called Onvansertib to see if it can help people with a tough type of blood cancer called chronic myelomonocytic leukemia (CMML) that hasn't responded to other treatments, especially for those with specific gene changes.
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.