T cell acute lymphoblastic leukemia accumulation in the central nervous system
Susan Schwab
PhDNew York University School of Medicine
Project Term: July 1, 2020 - June 30, 2024
T cell acute lymphoblastic leukemia (T-ALL) has a strong tendency to infiltrate the central nervous system (CNS). The goal is hope to develop strategies to treat CNS disease in T-ALL with less neurotoxicity and more efficacy than current chemotherapy.
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. While recent chemotherapy regimes have improved the overall survival rate, substantial challenges remain in treating the disease. One major issue is that ALL cells frequently invade the fluid that bathes the brain and spinal cord (the central nervous system, CNS). Prior to the use of therapies that specifically target leukemia in the CNS, over half of patients developed clinical signs of CNS leukemia. While both the B- and T-subtypes of ALL have a predilection for spreading to the CNS, T-ALL, in particular, is associated with CNS disease. Consequently, all children diagnosed with T-ALL receive chemotherapy designed to eradicate disease in the CNS. Although successful in extending life expectancy, CNS-directed chemotherapy is associated with significant toxicity, with lasting effects on learning and memory. Additionally, we have yet to eradicate CNS relapse. Thus, there is an urgent need to understand how T-ALL infiltrates the CNS and to develop novel strategies to target CNS disease. Here we will ask what “sign-posts” lead leukemia cells into the CNS, as these could potentially be targeted to limit CNS disease. We will also ask what enables leukemia cells to survive within the CNS, which is traditionally thought to have limited nutrient availability and is therefore a surprising location for leukemia cells to colonize. Finally, we will ask what, if any, is the immune response to leukemia in the CNS, in the hopes that we may be able to augment the ability of the immune system to combat leukemia. Taken together, the results of our studies will provide critical insight into treatment of this devastating disease.
This Discovery award is sponsored through a partnership between LLS, the Mark Foundation for Cancer Research and The Paul G. Allen Frontiers Group.