Show simple item record

dc.contributor.authorMuñoz-López, Alvaro
dc.contributor.authorRomero-Moya, Damià
dc.contributor.authorPrieto, Cristina
dc.contributor.authorRamos-Mejía, Verónica
dc.contributor.authorAgraz-Doblas, Antonio
dc.contributor.authorVarela, Ignacio
dc.contributor.authorBuschbeck, Marcus
dc.contributor.authorPalau, Anna
dc.contributor.authorCarvajal-Vergara, Xonia
dc.contributor.authorGiorgetti, Alessandra
dc.contributor.authorFord, Anthony
dc.contributor.authorLako, Majlinda
dc.contributor.authorGranada, Isabel
dc.contributor.authorRuiz-Xivillé, Neus
dc.contributor.authorRodriguez Perales, Sandra 
dc.contributor.authorTorres-Ruiz Raul, Raul 
dc.contributor.authorStam, Ronald W
dc.contributor.authorFuster, Jose Luis
dc.contributor.authorFraga, Mario F
dc.contributor.authorNakanishi, Mahito
dc.contributor.authorCazzaniga, Gianni
dc.contributor.authorBardini, Michela
dc.contributor.authorCobo, Isabel
dc.contributor.authorBayon, Gustavo F
dc.contributor.authorFernandez, Agustín F
dc.contributor.authorBueno, Clara
dc.contributor.authorMenendez, Pablo
dc.date.accessioned2019-10-30T10:04:21Z
dc.date.available2019-10-30T10:04:21Z
dc.date.issued2016-10-11
dc.identifier.citationStem Cell Reports. 2016;7(4):602-618.es_ES
dc.identifier.issn22136711es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8534
dc.description.abstractInduced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming "boosters" also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency.es_ES
dc.description.sponsorshipThis work was supported by the European Research Council to P.M. (ERC-2014-CoG-646903), the ISCIII/FEDER (E-Rare-2 Call PI12/03112 to P.M. and PI14/01191 to C.B.), MINECO (SAF2013-43065 to P.M.), and the Spanish Association Against Cancer (AECC) to P.M. and C.B. C.B. is supported by a Miguel Servet II contract (CPII13/00011). D.R.M. and A.M.-L. are supported by PFIS (FI11/0511) and FPI (BES-2014-067844) scholarships, respectively. P.M. also acknowledges financial support from the Obra Social La Caixa, Fundacio Josep Carreras and The Generalitat de Catalunya (SGR330). C.B. and P.M. are investigators of TERCEL.es_ES
dc.language.isoenges_ES
dc.publisherCell Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectB-ALLes_ES
dc.subjectDNA methylomees_ES
dc.subjectMLL-AF4es_ES
dc.subjectSendai viruses_ES
dc.subjectcancer reprogramminges_ES
dc.subjectiPSCes_ES
dc.subjecttranscriptomees_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBiomarkers es_ES
dc.subject.meshCell Line, Transformed es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Transdifferentiation es_ES
dc.subject.meshCluster Analysis es_ES
dc.subject.meshDNA Methylation es_ES
dc.subject.meshGene Expression es_ES
dc.subject.meshGene Expression Profiling es_ES
dc.subject.meshHematopoietic Stem Cells es_ES
dc.subject.meshHeterografts es_ES
dc.subject.meshHumans es_ES
dc.subject.meshInduced Pluripotent Stem Cells es_ES
dc.subject.meshMice es_ES
dc.subject.meshMyeloid Progenitor Cells es_ES
dc.subject.meshMyeloid-Lymphoid Leukemia Protein es_ES
dc.subject.meshOncogene Proteins, Fusion es_ES
dc.subject.meshPhenotype es_ES
dc.subject.meshPrecursor B-Cell Lymphoblastic Leukemia-Lymphoma es_ES
dc.subject.meshPrecursor Cells, B-Lymphoid es_ES
dc.subject.meshTranscriptome es_ES
dc.subject.meshTranslocation, Genetic es_ES
dc.subject.meshCellular Reprogramming es_ES
dc.subject.meshGene Rearrangement es_ES
dc.titleDevelopment Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotencyes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID27666791es_ES
dc.format.volume7es_ES
dc.format.number4es_ES
dc.format.page602-618es_ES
dc.identifier.doi10.1016/j.stemcr.2016.08.013es_ES
dc.contributor.funderEuropean Research Council (ERC)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIII (España)es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderAsociación Española Contra el Cáncer (España)es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderFundación La Caixaes_ES
dc.contributor.funderFundacio Josep Carrerases_ES
dc.contributor.funderGeneralitat de Catalunyaes_ES
dc.contributor.funderICREAes_ES
dc.contributor.funderBiotechnology and Biological Sciences Research Council (BBSRC)es_ES
dc.contributor.funderMedical Research Council UK (MRC)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2213-6711es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.stemcr.2016.08.013.es_ES
dc.identifier.journalStem cell reportses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Citogenética Moleculares_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI14/01191es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI12/03112es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2013-43065es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/CPII13/00011es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/FI11/0511es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/BES-2014-067844es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/EC/H2020/646903es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail
Acceso Abierto
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional