Dissecting CBFA2T3-GLIS2 Fusion-Driven Leukemogenesis and Therapeutic Resistance

Dr. Brandon Hadland, M.D. – Fred Hutchinson Cancer Center, Seattle, WA

Some types of childhood leukemia begin before birth, when early blood cells develop harmful genetic changes. One especially aggressive form, called CBFA2T3-GLIS2 acute megakaryocytic leukemia, is difficult to treat because it often resists chemotherapy and comes back after treatment. This project aims to understand how this leukemia starts and why it returns. Dr. Hadland’s team will use advanced lab models to mimic how the disease originates in early blood cells and transforms over time to frank leukemia. By studying these models, they hope to discover how leukemia cells grow, survive treatment, and change over time. The research has two main goals: first, to find ways to stop leukemia before it becomes dangerous, and second, to identify and eliminate the cells that survive treatment and cause relapse. The team will use powerful tools to track individual cells and uncover weak points that could be targeted with new therapies. This work could lead to better treatments and even ways to prevent leukemia in children who are at risk. In the future, it may be possible to detect genetic changes associated with these leukemias at birth and treat children early—before the disease ever develops.