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Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures Public Deposited

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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 intercompartmental 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.
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  • Lee, S. T., Muench, M. O., Fomin, M. E., Xiao, J., Zhou, M., de Smith, A., ... & Wiemels, J. L. (2015). Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures. Nucleic Acids Research, 43(5), 2590-2602. doi:10.1093/nar/gkv103
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  • 43
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  • 5
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  • National Institute of Environmental Health Sciences(NIEHS) and Environmental Protection Agency (EPA)[P01ES018172]; NIEHS [R01ES09137, P42ES04705]; NationalCancer Institute (NCI) [R01CA155461]; Tobacco-Related Disease Research Program[18CA-0127]; Leukemia and Lymphoma Society [6026-10]. Funding for open accesscharge: NIH.
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  • description.provenance : Made available in DSpace on 2015-05-20T17:39:08Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) HousemanEugenePHHSEpigeneticRemodelingB-Cell.pdf: 2219562 bytes, checksum: 76a86a1eeb4ce1eaaecb812b25aa1c64 (MD5) HousemanEugenePHHSEpigeneticRemodelingB-Cell_SupplementaryData.zip: 4173499 bytes, checksum: fbf7dc8ead51ff5d86addba751a4ea5c (MD5) Previous issue date: 2015-03-11
  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2015-05-20T17:38:41Z No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) HousemanEugenePHHSEpigeneticRemodelingB-Cell.pdf: 2219562 bytes, checksum: 76a86a1eeb4ce1eaaecb812b25aa1c64 (MD5) HousemanEugenePHHSEpigeneticRemodelingB-Cell_SupplementaryData.zip: 4173499 bytes, checksum: fbf7dc8ead51ff5d86addba751a4ea5c (MD5)
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2015-05-20T17:39:08Z (GMT) No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) HousemanEugenePHHSEpigeneticRemodelingB-Cell.pdf: 2219562 bytes, checksum: 76a86a1eeb4ce1eaaecb812b25aa1c64 (MD5) HousemanEugenePHHSEpigeneticRemodelingB-Cell_SupplementaryData.zip: 4173499 bytes, checksum: fbf7dc8ead51ff5d86addba751a4ea5c (MD5)

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