Investigators will undertake laboratory studies to determine the molecular processes that lead cancerous white blood cells to infiltrate the brain in the disease called T cell acute lymphoblastic leukemia (T-ALL), in an effort to prevent the severe cognitive consequences of this cancer and enhance treatment in children and adolescents.

T-ALL is a blood cancer that primarily afflicts children and adolescents.  Cancerous “lymphocytic” white blood cells infiltrate the central nervous system (CNS, the brain, and spinal cord) at the diagnostic stage, and also—in about 30 percent of children and adolescents—following treatment, as the disease relapses in the brain and spinal cord.  Physicians aggressively use radiation therapy of the skull and chemotherapy, therefore, as a strategy to prevent CNS involvement initially and following treatment.  The strategy has improved outcomes, but at great cost.  Side-effects can include brain tumors, developmental delay, or mental retardation.  The frequency of these brain consequences has intensified efforts to identify the signaling pathways and genes responsible for leading the cancerous, lymphocytic white blood cells into the brain.

New York University investigators have identified a single gene that controls blood cell migration and adhesion (sticking together) and have determined that this gene is essential for enabling leukemia cells to invade the brain.  The gene produces a specific receptor for “chemokines,” proteins that prompt white blood cells to move.  In fact, when this single gene called “CCR7” is inactivated, leukemic white blood cells are unable to infiltrate the CNS.  Now the investigators will undertake laboratory studies in an animal model of T-ALL—including imaging and gene targeting techniques—and studies in patients’ cancer cells, to understand the molecular processes that the gene uses to lead leukemic blood cells into the CNS.

Significance: Understanding the molecular processes that the CCR7 gene uses to lead leukemic white blood cells into the CNS will be critical to determining how to block them and prevent CNS devastation from this cancer and its treatment.