Admixture analysis of acute lymphoblastic leukemia in African American children: the ADMIRAL Study

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Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as “NOT-CA- 22-057”. In our parent project titled “Admixture analysis of acute lymphoblastic leukemia (ALL) in African American children (ADMIRAL Study; R01CA239701), we are performing admixture mapping to identify ancestral genomic loci that may account for differential risk and unfavorable clinical phenotypes of ALL in African American (AA) children. In this Administrative Supplement Opportunity to Stimulate or Strengthen Global Cancer Health Disparities Research, we propose synergistic molecular epidemiology research to identify leukemia biology factors that potentially underly the same clinical problem (unfavorable ALL phenotypes) among children in Africa. The high burden of childhood ALL and urgent importance to effectively control the cancer in Africa is highlighted by the World Health Organization’s Global Initiative for Childhood Cancer. The goal of the proposed supplemental research project is to leverage this African childhood ALL cohort as a triangulating comparator that shares genetic ancestry with AA but lacks European admixture and has a distinctively different landscape of environmental immune challenges, namely, endemic viral infections. The purpose is to identify the biological underpinnings of unfavorable ALL prognostic factors in AA and African children that can be targeted to reduce ALL survival disparities in these populations. Our overarching approach is to characterize somatic, inherited, and environmental determinants of clinical differences in childhood ALL among world populations; the Specific Aims are to: 1. Identify the cytogenetic abnormalities that may underpin unfavorable ALL clinical phenotypes among children of African ancestry and their association with African/European genetic admixture. 2. Compare the prevalence of replicated inherited single nucleotide variants (SNVs) that are reported in the literature to be associated with ALL risk and outcomes among African, AA and EA children. 3. Characterize the plasma exogenous virome in children with ALL in Africa.