Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures
Year: 2015
Type: article
Study design: Observational Study
Abstract: We investigated DNA methylomes of pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. Epigenetic alteration of B-ALLs occurred in two tracks: de novo methylation of small functional compartments and demethylation of large inter-compartmental backbones. The deviations were exaggerated in lamina-associated domains, with differences corresponding to methylation clusters and/or cytogenetic groups. Our data also suggested a pivotal role of polycomb and CTBP2 in de novo methylation, which may be traced back to bivalency status of embryonic stem cells. Driven by these potent epigenetic modulations, suppression of polycomb target genes was observed along with disruption of developmental fate and cell cycle and mismatch repair pathways and altered activities of key upstream regulators.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkv103
Institutions: University of California, San Francisco, Yonsei University, Yonsei University Health System, Blood Systems Research Institute, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Centro Nacional de Análisis Genómico, Parc Científic de Barcelona, Oregon State University, University of California, Berkeley
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Awards: Environmental and Molecular Epidemiology of Childhood Leukemia, Genome-Wide Association Study of Childhood Leukemia by Hispanic Status, Center for Integrative Research on Childhood Leukemia and the Environment, G5155614440, G7406788737, Development of iPS Cells for Treatment of Hemoglobinopathies, Toxic substances in the environment
OpenAlex ID: W2098958008