Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Acute lymphoblastic leukemia (ALL) is a cancer where the bone marrow makes too many lymphocytes (a type of white blood cell) and is the most common childhood cancer. Roughly 5% of ALL cases feature a reciprocal translocation between chromosomes 1 and 19 [t(1;19)], resulting in the creation of a defective gene. Current therapeutic regimens are non-specific, biologically crude and highly toxic; therefore, novel therapeutic regimens with increased specificity and decreased toxicity must be developed. The biological mechanisms underlying these leukemias are poorly understood to date. In order for new treatments to be designed, a thorough understanding of the biological mechanisms behind the disease is required. This proposal is primarily aimed at increasing our understanding of this disease. The hallmarks of ALL cancer cells (lymphoblasts) include blocked cell maturation and increased proliferation relative to normal cells. Since the lymphoblasts are blocked in maturation, they do not undergo cell death like normal cells and accumulate in the bone marrow. I propose to investigate the biological mechanisms behind the maturation block in this particular type of leukemia. Once we understand how the cells are blocked in maturation, new therapies can be designed that liberate the cells from the maturational block and allow them to develop into mature lymphocytes. This will result in the reduction of lymphoblasts and thus regression of the cancer. Similar strategies have been successfully developed for acute promyelocytic leukemia. Our hope is that the development of a more specific treatment will result in reduced side effects from radiation and chemotherapy and also lead to increased treatment success rate.