Blocking AMP production to overcome drug resistance in acute myeloid leukemia
Targeting AMP Synthesis to Overcome Resistance to BH3 Mimetics in Acute Myeloid Leukemia
Researchers are testing whether blocking an enzyme that makes AMP can help venetoclax-based treatment work again for older adults with resistant acute myeloid leukemia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Beckman Research Institute/city of Hope NIH-funded |
| Lab location | 1 site (Duarte, United States) |
| Project ID | NIH-11300248 on NIH RePORTER |
What this research studies
This project focuses on older adults with AML whose disease has become resistant to venetoclax plus azacytidine. Scientists found that leukemia cells upregulate an enzyme called ADSS2 that increases AMP production and activates AMPK signaling to protect mitochondria from drug-induced death. Using CRISPR genetic screens, patient-derived xenograft models, and a lab-made ADSS inhibitor, the team will test whether blocking ADSS2 restores mitochondrial cell death and clears resistant leukemia in preclinical models. The goal is to create a rationale for future combination treatments that could be offered to patients.
Who could benefit from this research
Good fit: Adults with acute myeloid leukemia—especially older patients (≥60)—who have relapsed or whose disease is resistant to venetoclax-based therapy would be the ideal candidates.
Not a fit: Patients whose leukemia is well controlled by current therapy, whose resistance is driven by unrelated mechanisms, or people with other types of cancer are unlikely to benefit directly from this project.
Why it matters
Potential benefit: If successful, this work could restore sensitivity to venetoclax-based therapy in patients with AML who have developed resistance, enabling new combination treatment options.
How similar studies have performed: Venetoclax plus hypomethylating agents has improved outcomes for older AML patients in clinical practice, but targeting AMP synthesis via ADSS2 is a new approach with promising results so far only in preclinical studies.
Where this research is happening
Duarte, United States
- Beckman Research Institute/city of Hope — Duarte, United States (Active)
Researchers
- Principal investigator: Li, Ling — Beckman Research Institute/city of Hope
- Study coordinator: Li, Ling
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.