Keck School of Medicine and Center for Genetic Epidemiology researcher Adam de Smith has received funding toward studying the causes and early-life origins of acute lymphoblastic leukemia (ALL). The $600,000 five-year Scholar Award is from the Career Development Program within the Leukemia & Lymphoma Society, which supports up-and-coming leaders in blood cancer research.
As the most common cancer in children, ALL is a leading cause of childhood mortality and morbidity, with those that survive often facing long-term chronic health conditions resulting from undergoing chemotherapy.
De Smith’s goal is to understand what causes this type of cancer in children, aiming to inform and facilitate newborn screening to identify the most at-risk children. He hopes these children could then benefit from targeted preventive strategies.
“Prevention of childhood ALL remains the ultimate goal, but this will only be achievable by determining its causes, by understanding its natural history, and by identifying children with the greatest risk of developing the disease,” says de Smith.
During the project, de Smith will conduct epidemiological studies of the disease in Hispanic/Latino children, and children with Down syndrome, in order to discover potential genetic predisposition. These populations are particularly susceptible to ALL – Hispanic/Latino children have up to a 40% increased chance of developing ALL when compared to non-Hispanic white children, and children with Down syndrome have an over 20-fold chance of developing ALL when compared to children without Down syndrome.
“Determining the genetic contribution to ALL risk in these populations will inform our understanding of ALL etiology in general and is essential for future risk stratification in these vulnerable populations,” says de Smith.
De Smith will also look at data from newborns, to learn if the disease or indicators of susceptibility to the disease can be detectable at birth. To do this, de Smith has partnered with the Children’s Oncology Group, and investigators at the University of Minnesota and the University of Oxford, to collect banked cord blood samples from childhood ALL patients. With this data, de Smith and collaborators on the ReCord Study hope to characterize which leukemia mutations develop before birth, what are the cells of origin of childhood leukemia, and whether there are risk factors associated with the development and frequency of these “preleukemic” mutations.
“This is a unique resource and study design,” says de Smith. “It allows 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.”
De Smith hopes that his research could lead to a tangible change in the labor and delivery ward – screening newborns for preleukemia.
“Identifying newborns with preleukemia and assessing their chances of developing full-blown leukemia based on their genetics and other known risk factors may, for the first time, present opportunities for precision prevention strategies for childhood ALL,” says de Smith.