Role of PAX5 mutations in B-cell acute lymphoblastic leukemia

Dr. Zhaohui Gu – Beckman Research Institute of the City of Hope, Duarte, CA

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer and remains a leading cause of childhood cancer death. B-ALL includes dozens of subtypes driven by different genetic alterations and observed with different levels of risk. Therefore, understanding each B-ALL subtype is essential for developing and applying the optimal treatment for each patient. Around 10% of BALL are driven by mutations in PAX5, a key gene for B-cell development. This group of patients is observed with intermedia to high level of risk depending on the age groups and specific mutations. However, with limited understanding of this relative new leukemia subtype, generic chemotherapies are applied and the outcomes for many of them are still poor.

In this project, we will study the role of PAX5 mutations in regulating specific genes, biological pathways, B-cell development, and the initiation of leukemia. We will combine the high-throughput sequencing technologies and multiple experimental models to identify and validate the key players in leukemia development, and then test the potential of targeting these drivers to specifically kill leukemia cells. With the molecular markers and deregulated biological pathways identified through this study, a solid scientific framework will be established to advance our understanding of PAX5-mutant leukemia, develop efficacious targeted therapies, and ultimately lead to improved outcomes for this leukemia entity.