Leveraging Susceptible Populations and Unique Resources in a Pathway to Prevention of Childhood Acute Lymphoblastic Leukemia
Adam de Smith
PhDUniversity of Southern California
Project Term: July 1, 2023 - June 30, 2028
The focus of my research is to understand the causes and early-life origins of acute lymphoblastic leukemia (ALL). We use a two-pronged approach: 1) conducting epidemiological studies of ALL in susceptible populations to understand genetic predisposition, and 2) investigating the in utero origins of ALL across subtypes. Our goals are to identify children at the highest risk of developing ALL through genetic screening and to lay the groundwork for precision prevention strategies.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and remains a leading cause of childhood mortality. Further, survivors of childhood ALL face long-term chronic health conditions due to the harsh effects of chemotherapy treatment. Thus, prevention of childhood ALL remains the ultimate goal, but this will only be achievable by understanding its causes, by elucidating its natural history, and by identifying children with the greatest risk of developing ALL. The goals of my research program are to understand the causes of childhood ALL and how it first develops, and to lay the groundwork for prevention of this disease in at-risk children. Firstly, we study genetic risk factors – that is, differences in our DNA that make us more or less susceptible to developing disease – for childhood ALL in two particularly susceptible populations: 1) children of Hispanic/Latino ethnicity, by leveraging the unique resources of our studies based in California and collaborations with studies across the U.S. and Mexico; and 2) children with Down syndrome, a uniquely high-risk population who have a 20-fold increased risk of ALL than children without Down syndrome. Studying the variations in DNA that are associated with risk of ALL in these vulnerable children will shed light on the causes of ALL in the general population and will help us to identify children with the highest risk of developing ALL. Secondly, we aim to understand the early-life origins of ALL, capitalizing on the unique resources of the Children’s Oncology Group to collect banked cord blood samples from childhood ALL patients, which will allow us to examine which types of ALL develop during pregnancy, how the leukemia first develops many years prior to diagnosis, and what are the potential preventable risk factors for leukemia development in utero. Through these distinct but complementary research aims, we will gain a comprehensive knowledge of the genetic risk factors for childhood ALL so that we can identify children with the highest risk of developing the disease, and we will lay the groundwork towards newborn screening of leukemia and possible precision prevention strategies. The results of this research will benefit future blood cancer patients, by identifying novel therapeutic targets and by preventing ALL from ever developing in the first place in susceptible children.