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Title: Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures.
Author: Lee, Seung-Tae
Muench, Marcus O.
Fomin, Marina E.
Xiao, Jianqiao
Zhou, Mi
Smith, Adam de
Martín-Subero, José Ignacio
Heath, Simon
Houseman, E.Andres
Roy, Ritu
Wrensch, Margaret
Wiencke, John
Metayer, Catherine
Wiemels, J.L.
Keywords: Leucèmia
Cèl·lules mare embrionàries
Embryonic stem cells
Issue Date: 11-Mar-2015
Publisher: Oxford University Press
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.
Note: Reproducció del document publicat a:
It is part of: Nucleic Acids Research, 2015, vol. 43, num. 5, p. 2590-2602
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ISSN: 0305-1048
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)

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