Targeting RNA Condensates in Pediatric Myeloid Leukemia

Dr. Bruno Di Stefano, Ph.D. – Baylor College of Medicine, Houston, TX

Acute myeloid leukemia (AML), the second most common childhood leukemia, is an aggressive blood cancer driven by uncontrolled proliferation of immature white blood cells. Only 65% of children achieve long-term remission, despite intensive chemotherapy that results in harsh side effects and even death. We aim to discover alternative therapies by understanding what makes pediatric AML cells survive. Here, we found P-bodies to be crucial for pediatric AML cell survival. P-bodies are small particles within the cell that serve as reservoirs to store mRNAs and prevent them from guiding protein production. We discovered that a gene called DDX6, responsible for assembling P-bodies, is overexpressed in pediatric AML patients. Moreover, AML cells have more P-bodies compared to healthy blood cells. We further show that P-bodies are crucial for progression of pediatric AML. By isolating intact P-bodies from pediatric AML cells, we found that pediatric AML cells use them to hide mRNAs encoding key tumor suppressors, preventing them from exerting an anti-cancer effect. Therefore, targeting P-bodies could be a potential therapeutic approach for treating pediatric AML. Through our research, we aim to gain insights into how dysregulation of DDX6 and P-body assembly sustains pediatric AML. By understanding these mechanisms, we hope to develop more effective and targeted treatments, improving the lives of young patients and reducing the severe side effects associated with current therapies.