Aberrant DNA methylation constitutes a key feature of pediatric acute lymphoblastic leukemia at diagnosis, however its role as a predisposing or early contributor to leukemia development remains unknown.
Here, we evaluate DNA methylation at birth in 41 leukemia-discordant monozygotic twin pairs using the Illumina EPIC array on archived neonatal blood spots to identify epigenetic variation associated with development of pediatric acute lymphoblastic leukemia, independent of genetic influence.
Through conditional logistic regression we identify 240 significant probes and 10 regions associated with the discordant onset of leukemia.
Background Periconceptional folate intake is associated with the establishment of DNA methylation in offspring; however, variations in this relationship by food sources versus folic acid supplements are not described. Also, maternal folate intake is associated with decreased risk of pediatric acute lymphoblastic leukemia (ALL), but the mechanism is not known.
Objectives We evaluated the relationship between periconceptional folate intake by source and DNA methylation at birth in a cohort of pediatric ALL cases and controls in an epigenome-wide association study.
Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions.
We conducted a case-control study of 226 case child-mother pairs and 404 control child-mother pairs to evaluate the role of interaction between HLA genotypes in the offspring and maternal killer immunoglobulin-like receptor (KIR) genotypes in the etiology of childhood ALL, while considering potential mediation by neonatal cytokines and the immune-modulating enzyme arginase-II (ARG-II).
Genome-wide association studies have identified a growing number of single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL), yet the functional roles of most SNPs are unclear. Multiple lines of evidence suggest epigenetic mechanisms may mediate the impact of heritable genetic variation on phenotypes. Here, we investigated whether DNA methylation mediates the effect of genetic risk loci for childhood ALL. We performed an epigenome-wide association study (EWAS) including 808 childhood ALL cases and 919 controls from California-based studies using neonatal blood DNA.
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.
Abstract:
Infections and antigenic exposures during childhood are associated with pediatric acute lymphoblastic leukemia (ALL) and are thought to lead to immune dysregulation stimulating pre-leukemic clones to expand and progress to overt leukemia. Emerging epidemiologic and laboratory evidence suggests cytomegalovirus (CMV) may contribute to the development of childhood ALL inspiring further investigative efforts and for the first time, identifying a specific target for ALL prevention.
In this study, we aimed to better elucidate the role of CMV in ALL etiology by screening diagnostic leukemia bone marrow samples for CMV DNA using a highly quantitative droplet digital PCR (ddPCR) assay.
We performed a trans-ethnic GWAS of childhood ALL in a discovery panel of 76,317 individuals, including 3482 cases and 72,835 controls distributed across four ethnic cohorts (African Americans, AFR; East Asian Americans, EAS; Latino Americans, LAT; Non-Latino White Americans, NLW; Supplemen- tary Information). After quality control filtering, our dataset consisted of 124, 318, 1878, 1162 cases and 2067, 5017, 8410, 57,341 controls in AFR, EAS, LAT, and NLW, respectively. Furthermore, we tested the association at 7,628,894 imputed SNPs, including low frequency (minor allele frequency, MAF, between 1–5%) variants that were not previously systematically tested.
Background: Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases.
Methods: Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data.