Why some B‑cell lymphomas resist PRMT inhibitor drugs
Understanding resistance mechanisms to protein arginine methyltransransferase Inhibitors in Lymphoma
Researchers are exploring if targeting the MSI2 protein can help PRMT inhibitor drugs work better for adults with B‑cell non‑Hodgkin lymphoma.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sloan-Kettering Inst Can Research NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11284088 on NIH RePORTER |
What this research studies
This project uses lab‑grown lymphoma cells, genetically modified mice, and tumor samples from patients to understand why some B‑cell lymphomas resist new drugs that target PRMT enzymes. A genome‑wide CRISPR screen identified the RNA‑binding protein MSI2 as a top candidate driving resistance, so the team will study how MSI2 and PRMT1/PRMT5 interact. They will change MSI2 and PRMT activity in cells and mouse models and analyze protein modifications to see if reducing MSI2 improves drug response. Patient tumor samples will be used to link lab findings to real tumors and to inform possible future clinical trials.
Who could benefit from this research
Good fit: Adults with B‑cell non‑Hodgkin lymphoma, especially those with aggressive or relapsed disease or tumors showing high PRMT5 or MSI2 levels, would be the most relevant patients.
Not a fit: People without B‑cell lymphoma, or whose tumors lack PRMT/MSI2 involvement, and those not eligible for future clinical testing would likely not benefit directly from this work.
Why it matters
Potential benefit: If successful, this work could point to new combination approaches that make PRMT inhibitors effective for more lymphoma patients.
How similar studies have performed: Preclinical studies show PRMT5 inhibitors can slow lymphoma growth, but using MSI2 targeting to overcome resistance is a newer, mostly preclinical idea.
Where this research is happening
New York, United States
- Sloan-Kettering Inst Can Research — New York, United States (Active)
Researchers
- Principal investigator: Kharas, Michael — Sloan-Kettering Inst Can Research
- Study coordinator: Kharas, Michael
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.