How bone marrow signals and metabolism fuel T‑cell acute lymphoblastic leukemia
Molecular understanding of leukemic bone marrow cytokine-Ras signals and metabolic dependence
Researchers are looking at how abnormal Ras and cytokine signals in the bone marrow change leukemia cell behavior and whether targeting PI3K‑AKT metabolic pathways can help children and young adults with T‑cell ALL respond better to treatment.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11247990 on NIH RePORTER |
What this research studies
The team uses advanced mouse models that mimic human T‑cell ALL and analyzes bone marrow cells with multiplex flow cytometry to map how Ras and cytokine signals alter cell development. They run large drug‑combination (synthetic lethality) screens focused on PI3K pathway inhibitors and test predicted combinations in lab models. Early results showed different Ras alterations produce distinct leukemia behaviors and that combining PI3K inhibitors with standard chemotherapy drugs like vincristine produced strong killing of leukemia cells in preclinical tests. The aim is to turn these lab findings into targeted combination approaches that could make treatment more effective and less toxic for patients.
Who could benefit from this research
Good fit: Children and young adults with T‑cell acute lymphoblastic leukemia, especially those with Ras pathway mutations or relapsed/refractory disease, would be the most relevant candidates.
Not a fit: People with other leukemia types (for example B‑ALL), unrelated cancers, or healthy volunteers are unlikely to gain direct benefit from this work.
Why it matters
Potential benefit: Could identify targeted drug combinations that improve chemotherapy effectiveness and reduce relapse risk in T‑cell ALL patients.
How similar studies have performed: Preclinical studies, including work from this team, have shown promising synergy between PI3K pathway inhibitors and chemotherapy (for example GDC0941 plus vincristine), but clear clinical benefit in patients has not yet been established.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Roose, Jeroen — University of California, San Francisco
- Study coordinator: Roose, Jeroen
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.