Effects of CNS Treatment on Antioxidant Level, Apoptosis and Cognitive Abilities in Childhood Leukemia
Acute lymphoblastic leukemia (ALL) is the most common pediatric tumor in the United States, and survival is approximately 85%. Central nervous system (CNS) treatment with the methotrexate is necessary to prevent disease relapse in the brain, but frequently results in cognitive problems that have devastating effects on educational, behavioral, and quality of life outcomes. Despite evidence for cognitive problems following CNS treatment, little is known about how methotrexate damages normal brain tissue in these children. Findings from our animal study showed increased degeneration of neurons in specific brain regions, and changes in the expression of genes important for antioxidant production and programmed cell death (known as apoptosis). We want to translate these findings to a clinical study of children with ALL who receive CNS treatment with methotrexate. In this study we will determine if the level of the most important brain antioxidant (glutathione) and activity of several enzymes involved in programmed cell death (caspase enzymes) are associated with cognitive abilities in children with ALL. We are in an ideal position to carry out this study because we have frozen cerebrospinal fluid (fluid that circulates in brain tissue), and measures of cognitive abilities in a secure database. This study is highly relevant to pediatric cancer research because findings can provide information about how methotrexate causes brain injury that could be important for cognitive abilities. Findings will be used to test new interventions to protect the brain from injury, and hopefully improve cognitive outcomes among the increasing number of survivors of ALL.