Epigenomic mapping in B-cell acute lymphoblastic leukemia identifies transcriptional regulators and noncoding variants promoting distinct chromatin architectures [Hi-C]
Acute lymphoblastic leukemia (ALL) is the most common malignancy in pediatric patients and represents about a quarter of all pediatric malignancies. Past work has characterized B-cell lineage ALL (B-ALL) into molecular subtypes spanning a range of aberrant chromosomal rearrangements and oncogene chimeric fusions driving malignancy. While transcriptional and DNA methylome profiling of these subtypes has been extensively examined, the accompanying chromatin landscape and corresponding gene regulatory repertoire are not well characterized for many B-ALL subtypes. To better profile the B-ALL epigenome and gene regulatory networks we examined chromatin accessibility of 10 distinct molecular subtypes (BCR-ABL1, DUX4/ERG, ETV6-RUNX1, Hyperdiploid, Low hypodiploid, KMT2A-rearranged, Ph-like, PAX5-altered, TCF3-PBX1, ZNF384-rearranged and B-other) using 156 primary patient samples from across the United States with assay for transposase-accessible chromatin and high-throughput sequencing (ATAC-seq). In complement to ATAC-seq a subset of cell line and patient samples were profiled using promoter capture Hi-C to better define gene regulatory network connections. Overall design: Promoter capture HiC