Summary
Children with Down syndrome (DS), which occurs due to trisomy 21, have a 20-fold increased risk of acute lymphoblastic leukemia (ALL), but the basis for the increased risk of leukemia remains unclear, including the potential interplay between other DS phenotypic features and ALL susceptibility. This study will build upon our previous genome-wide association study, as well as our ongoing genomic profiling and phenotyping efforts, to: 1) perform a comprehensive analysis of heritable variation associated with risk of ALL in children with DS, with a focus on structural, rare, and chromosome 21 variants; and 2) conduct deep phenotyping of children with DS-ALL to identify the impact of DS-related phenotypes on leukemia susceptibility and outcomes. Findings from this study may lead to improved genetic testing and counseling strategies for children with DS, and insights into genes driving DS-ALL may guide development of targeted therapies to improve outcomes in this vulnerable and high-risk patient population.
Down Syndrome Publications
Nature communications2021
Birth defects research2021