dc.contributor.author | Muñoz-López, Alvaro | |
dc.contributor.author | Romero-Moya, Damià | |
dc.contributor.author | Prieto, Cristina | |
dc.contributor.author | Ramos-Mejía, Verónica | |
dc.contributor.author | Agraz-Doblas, Antonio | |
dc.contributor.author | Varela, Ignacio | |
dc.contributor.author | Buschbeck, Marcus | |
dc.contributor.author | Palau, Anna | |
dc.contributor.author | Carvajal-Vergara, Xonia | |
dc.contributor.author | Giorgetti, Alessandra | |
dc.contributor.author | Ford, Anthony | |
dc.contributor.author | Lako, Majlinda | |
dc.contributor.author | Granada, Isabel | |
dc.contributor.author | Ruiz-Xivillé, Neus | |
dc.contributor.author | Rodriguez Perales, Sandra | |
dc.contributor.author | Torres-Ruiz Raul, Raul | |
dc.contributor.author | Stam, Ronald W | |
dc.contributor.author | Fuster, Jose Luis | |
dc.contributor.author | Fraga, Mario F | |
dc.contributor.author | Nakanishi, Mahito | |
dc.contributor.author | Cazzaniga, Gianni | |
dc.contributor.author | Bardini, Michela | |
dc.contributor.author | Cobo, Isabel | |
dc.contributor.author | Bayon, Gustavo F | |
dc.contributor.author | Fernandez, Agustín F | |
dc.contributor.author | Bueno, Clara | |
dc.contributor.author | Menendez, Pablo | |
dc.date.accessioned | 2019-10-30T10:04:21Z | |
dc.date.available | 2019-10-30T10:04:21Z | |
dc.date.issued | 2016-10-11 | |
dc.identifier.citation | Stem Cell Reports. 2016;7(4):602-618. | es_ES |
dc.identifier.issn | 22136711 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8534 | |
dc.description.abstract | Induced 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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Cell Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | B-ALL | es_ES |
dc.subject | DNA methylome | es_ES |
dc.subject | MLL-AF4 | es_ES |
dc.subject | Sendai virus | es_ES |
dc.subject | Cancer reprogramming | es_ES |
dc.subject | iPSC | es_ES |
dc.subject | Transcriptome | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | Cell Line, Transformed | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | Cell Transdifferentiation | es_ES |
dc.subject.mesh | Cluster Analysis | es_ES |
dc.subject.mesh | DNA Methylation | es_ES |
dc.subject.mesh | Gene Expression | es_ES |
dc.subject.mesh | Gene Expression Profiling | es_ES |
dc.subject.mesh | Hematopoietic Stem Cells | es_ES |
dc.subject.mesh | Heterografts | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Induced Pluripotent Stem Cells | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Myeloid Progenitor Cells | es_ES |
dc.subject.mesh | Myeloid-Lymphoid Leukemia Protein | es_ES |
dc.subject.mesh | Oncogene Proteins, Fusion | es_ES |
dc.subject.mesh | Phenotype | es_ES |
dc.subject.mesh | Precursor B-Cell Lymphoblastic Leukemia-Lymphoma | es_ES |
dc.subject.mesh | Precursor Cells, B-Lymphoid | es_ES |
dc.subject.mesh | Transcriptome | es_ES |
dc.subject.mesh | Translocation, Genetic | es_ES |
dc.subject.mesh | Cellular Reprogramming | es_ES |
dc.subject.mesh | Gene Rearrangement | es_ES |
dc.title | Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 27666791 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 4 | es_ES |
dc.format.page | 602-618 | es_ES |
dc.identifier.doi | 10.1016/j.stemcr.2016.08.013 | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Asociación Española Contra el Cáncer | |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Fundación La Caixa | |
dc.contributor.funder | Fundación Josep Carreras Contra la Leucemia | |
dc.contributor.funder | Government of Catalonia (España) | |
dc.contributor.funder | Institució Catalana de Recerca i Estudis Avançats | |
dc.contributor.funder | Biotechnology and Biological Sciences Research Council (Reino Unido) | |
dc.contributor.funder | Medical Research Council (Reino Unido) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2213-6711 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.stemcr.2016.08.013. | es_ES |
dc.identifier.journal | Stem cell reports | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Unidades técnicas::Unidad de Citogenética Molecular | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/PI14/01191 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/PI12/03112 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2013-43065 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/CPII13/00011 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/FI11/0511 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/BES-2014-067844 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/EC/H2020/646903 | es_ES |
dc.rights.accessRights | open access | es_ES |