Precision Epigenetic Therapies for Pediatric Burkitt Lymphoma
Dr. Darko Barisic, Ph.D. – Weill Medical College of Cornell University, New York, NY
Burkitt lymphoma is one of the fastest growing childhood cancers, yet children who relapse have very limited treatment options. This project focuses on a newly discovered weakness in Burkitt lymphoma: mutations in the BAF complex, a group of proteins that normally control how DNA is packaged and which genes are turned on or off. More than half of children with Burkitt lymphoma carry these mutations, which change how immune cells develop and make them more likely to become cancerous. We hypothesize that when these genetic changes co-occur together with chronic inflammation, such as from virus infection or even diet-related inflammation, immune cells are prone to enter a dangerous cycle of repeated growth and mutation. This sets the stage for lymphoma to form and progress. We have identified a new drug that blocks the altered BAF complex and selectively kills Burkitt lymphoma cells with these mutations, while sparing normal cells. In this project we will use advanced models and engineered pediatric lymphoma cells to learn exactly how BAF mutations and inflammation cooperate to drive cancer. We will also test whether combining BAF inhibitors with anti-inflammatory or immune-based therapies can more effectively eliminate tumors. The goal is to create precision treatments for children with Burkitt lymphoma, especially those with relapsed or high-risk disease. We aim to develop safer and more effective therapies that improve survival and quality of life for young patients.
