Genetic determinants of lymphocyte traits and risk of acute lymphoblastic leukemia in children with Down syndrome

Children with Down syndrome (DS) have a high risk of developing acute lymphoblastic leukemia (ALL), and DS- ALL patients have inferior clinical outcomes than ALL patients without DS. We will perform a comprehensive study of the role of genetic variation in blood cell traits in the etiology of DS-ALL, including examining the causal effects of a genetic propensity for overproduction of lymphocytes on DS-ALL risk, and assessing whether blood cell trait-associated genetic variants are associated with somatic features and clinical outcomes in DS-ALL patients. Our results will help to identify children with DS most at risk of developing ALL, and may highlight novel intervention strategies to prevent DS-ALL and reduce adverse patient outcomes.