Role of Protocadherin-9 in Enabling Leukemia Cell Colonization of the CNS
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Current therapies lead to high remission rates, but many patients relapse, often with involvement of the brain and spinal cord – the Central Nervous System (CNS). Specific CNS-directed treatments limit these CNS relapses but do not eliminate them. Additionally, these CNS-directed treatments have severe short- and long-term side effects, particularly in children.
Our goal is to prevent relapses by inhibiting the ability of leukemia cells to colonize the CNS. Instead of using toxic treatments to kill the leukemia cells in the CNS (such as radiation or chemotherapy delivered directly to the brain and spinal cord), our work aims to stop leukemia colonization of the CNS by inhibiting proteins that enable leukemia cells to enter the brain and spinal cord and grow there. We have identified a candidate protein that is selectively present on the surface of leukemia cells that invade the CNS. We will determine if inhibiting this protein can prevent or reverse CNS colonization by leukemia cells and stop CNS relapses, thereby improving long-term survival. Inhibiting CNS colonization by leukemia cells would be a valuable tool to reduce leukemia relapse and could significantly improve patients’ quality of life by reducing or eliminating the need for CNS-directed therapies that have serious side-effects in pediatric patients.