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dc.contributor.authorGarcía Alegría, E.es_ES
dc.contributor.authorLafita Navarro, María Carmenes_ES
dc.contributor.authorAguado, R.es_ES
dc.contributor.authorGarcía Gutiérrez, Lucíaes_ES
dc.contributor.authorSarnataro, Kylees_ES
dc.contributor.authorRuiz Herguido, C.es_ES
dc.contributor.authorMartín, F.es_ES
dc.contributor.authorBigas, Annaes_ES
dc.contributor.authorCanelles, M.es_ES
dc.contributor.authorLeón Serrano, Javier es_ES
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2017-05-22T17:15:24Z
dc.date.available2017-05-22T17:15:24Z
dc.date.issued2016es_ES
dc.identifier.issn0304-3835es_ES
dc.identifier.urihttp://hdl.handle.net/10902/11025
dc.description.abstractChronic myeloid leukemia (CML) progresses from a chronic to a blastic phase, where the leukemic cells are proliferative and undifferentiated. The CML is nowadays successfully treated with BCR-ABL kinase inhibitors as imatinib and its derivatives. NUMB is an evolutionary well-conserved protein initially described as a functional antagonist of NOTCH function. NUMB is an endocytic protein associated with receptor internalization, involved in multiple cellular functions. It has been reported that MSI2 protein, a NUMB inhibitor, is upregulated in CML blast crisis, whereas NUMB itself is downregulated. This suggest that NUMB plays a role in the malignant progression of CML. Here we have generated K562 cells (derived from CML in blast crisis) constitutively expressing a dominant negative form of NUMB (dnNUMB). We show that dnNUMB expression confers a high proliferative phenotype to the cells. Importantly, dnNUMB triggers a partial resistance to imatinib in these cells, antagonizing the apoptosis mediated by the drug. Interestingly, imatinib resistance is not linked to p53 status or NOTCH signaling, as K562 lack p53 and imatinib resistance is reproduced in the presence of NOTCH inhibitors. Taken together, our data support the hypothesis that NUMB activation could be a new therapeutic target in CML.es_ES
dc.format.extent8 p.es_ES
dc.language.isoenges_ES
dc.publisherElsevier Science Irelandes_ES
dc.rights© 2016, Elsevier. Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivadaes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.sourceCancer Lett. 2016 May 28;375(1):92-9es_ES
dc.titleNUMB inactivation confers resistance to imatinib in chronic myeloid leukemia cellses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherVersionhttps://doi.org/10.1016/j.canlet.2016.02.037es_ES
dc.rights.accessRightsopenAccesses_ES
dc.identifier.DOI10.1016/j.canlet.2016.02.037es_ES
dc.type.versionacceptedVersiones_ES


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© 2016, Elsevier. Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivadaExcept where otherwise noted, this item's license is described as © 2016, Elsevier. Licensed under the Creative Commons Reconocimiento-NoComercial-SinObraDerivada