β-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1.
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- dc.contributor.author Gekas, Christosca
- dc.contributor.author Teresa, D'Altri 1984-ca
- dc.contributor.author Aligué, Rosaca
- dc.contributor.author González, Jessicaca
- dc.contributor.author Espinosa Blay, Lluísca
- dc.contributor.author Bigas Salvans, Annaca
- dc.date.accessioned 2016-10-24T09:06:49Z
- dc.date.issued 2016
- dc.description.abstract Notch activation is instrumental in the development of most T-cell acute lymphoblastic leukemia (T-ALL) cases, yet Notch mutations alone are not sufficient to recapitulate the full human disease in animal models. We here found that Notch1 activation at the fetal liver (FL) stage expanded the hematopoietic progenitor population and conferred it transplantable leukemic-initiating capacity. However, leukemogenesis and leukemic-initiating cell capacity induced by Notch1 was critically dependent on the levels of β-Catenin in both FL and adult bone marrow contexts. In addition, inhibition of β-Catenin compromised survival and proliferation of human T-ALL cell lines carrying activated Notch1. By transcriptome analyses, we identified the MYC pathway as a crucial element downstream of β-Catenin in these T-ALL cells and demonstrate that the MYC 3' enhancer required β-Catenin and Notch1 recruitment to induce transcription. Finally, PKF115-584 treatment prevented and partially reverted leukemogenesis induced by active Notch1.ca
- dc.description.sponsorship This research was funded by the Worldwide Cancer Research (formerly AICR, 13-0064), Fundación AECC (Cancer infantil), Ministerio de Economía y Competitividad (SAF2013-40922-R), Red Temática de Investigación Cooperativa en Cáncer (RD12/0036/0054), Agència de Gestió d’Ajuds Universitaris i de Recerca (AGAUR) (2014SGR-124) to AB
- dc.format.mimetype application/pdfca
- dc.identifier.citation Gekas C, D'Altri T, Aligué R, González J, Espinosa L, Bigas A. β-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1. Leukemia. 2016 Oct;30(10):2002-2010. doi: 10.1038/leu.2016.106ca
- dc.identifier.doi http://dx.doi.org/10.1038/leu.2016.106
- dc.identifier.issn 0887-6924
- dc.identifier.uri http://hdl.handle.net/10230/27424
- dc.language.iso engca
- dc.publisher Nature Publishing Groupca
- dc.relation.ispartof Leukemia. 2016 Oct;30(10):2002-10
- dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/leu.2016.106ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Leucèmia aguda -- Aspectes genèticsca
- dc.title β-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1.ca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca