Down syndrome (DS) is caused by constitutional trisomy of chromosome 21 and is associated with an up to 30-fold increased risk of acute lymphoblastic leukemia (ALL). While DS is associated with alterations in epigenetic markers, including DNA methylation, and gene expression. These mechanisms have not been fully explored in relation to DS-ALL etiology. Because the epigenome is sensitive to genetic and environmental influences during fetal development and can be leveraged to characterize blood cell proportions, we sought to evaluate the role of the neonatal methylome in children with DS on subsequent ALL risk.
Background: Down syndrome (DS) is associated with an up to 30-fold increased risk of B-cell acute lymphoblastic leukemia (ALL), and DS-ALL patients have worse overall survival and increased long-term treatment-related health conditions compared with non-DS ALL patients. In a recent genome-wide association study of DS-ALL, established ALL genetic risk loci were associated with DS-ALL, with several single nucleotide polymorphisms (SNPs) conferring a larger effect on ALL risk in the context of DS than in euploidy.