Interplay between Genetic Ancestry, Self-reported Race and Ethnicity, and Clinical Factors in Pediatric Acute Lymphoblastic Leukemia: A REDIAL Consortium Report.
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BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) is the most common cancer in children, and its incidence and outcomes vary by race and ethnicity. METHODS: The Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium has assembled a cohort of patients <25 years at diagnosis to examine genetic and neighborhood-level factors influencing ALL. As the cohort is ongoing, for this report, we examined sociodemographic and cytogenetic factors that might be associated with ALL outcome disparities. RESULTS: Among 2,512 patients diagnosed between 2005 and 2020, we observed distinct patterns of genetic ancestry and residential characteristics across self-reported race and ethnicity. Latino children, who comprised 55.3% of the cohort, had a mean Amerindigenous ancestry proportion of 50.9%, whereas non-Latino White children exhibited a predominantly European ancestry (mean = 78%). Neighborhood-level analysis revealed significant socioeconomic and geographic differences by race/ethnicity, with Latino children more frequently residing in Latino enclaves or economically disadvantaged neighborhoods. Cytogenetic profiling of 551 patients showed that favorable subtypes (double trisomies and ETV6::RUNX1) predominated overall, but ETV6::RUNX1 was significantly less common in Latino than in non-Latino White children; conversely, CRLF2 overexpression and immunoglobulin heavy chain (IGH) rearrangements were more frequent among Latino children. CONCLUSIONS: This first REDIAL cohort analysis reveals how genetic ancestry and neighborhood-level factors jointly shape the distribution of ALL cytogenetic subtypes, advancing our understanding of contributors to disparities in ALL outcomes. IMPACT: This analysis offers insights into factors underlying disparities in ALL outcomes that may be targeted for mitigation, ultimately guiding more equitable approaches to risk stratification and intervention.