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dc.contributor.authorMuñoz-López, A
dc.contributor.authorRomero-Moya, D
dc.contributor.authorPrieto, C
dc.contributor.authorRamos-Mejía, V
dc.contributor.authorAgraz-Doblas, A
dc.contributor.authorVarela, I
dc.contributor.authorBuschbeck, M
dc.contributor.authorPalau, A
dc.contributor.authorCarvajal-Vergara, X
dc.contributor.authorGiorgetti, A
dc.contributor.authorFord, A
dc.contributor.authorLako, M
dc.contributor.authorGranada, I
dc.contributor.authorRuiz-Xivillé, N
dc.contributor.authorRodríguez-Perales, S
dc.contributor.authorTorres-Ruíz, R
dc.contributor.authorStam, RW
dc.contributor.authorFuster, JL
dc.contributor.authorFraga, MF
dc.contributor.authorNakanishi, M
dc.contributor.authorCazzaniga, G
dc.contributor.authorBardini, M
dc.contributor.authorCobo, I
dc.contributor.authorBayon, GF
dc.contributor.authorFernandez, AF
dc.contributor.authorBueno, C
dc.contributor.authorMenendez, P
dc.date.accessioned2017-01-10T12:59:38Z
dc.date.issued2016-10
dc.identifier.citationStem cell reports, 2016, 7 (4), pp. 602 - 618
dc.identifier.issn2213-6711
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/385
dc.identifier.eissn2213-6711
dc.identifier.doi10.1016/j.stemcr.2016.08.013
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.
dc.formatPrint-Electronic
dc.format.extent602 - 618
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectHematopoietic Stem Cells
dc.subjectMyeloid Progenitor Cells
dc.subjectCell Line, Transformed
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectTranslocation, Genetic
dc.subjectOncogene Proteins, Fusion
dc.subjectCluster Analysis
dc.subjectGene Expression Profiling
dc.subjectDNA Methylation
dc.subjectGene Expression
dc.subjectGene Rearrangement
dc.subjectPhenotype
dc.subjectMyeloid-Lymphoid Leukemia Protein
dc.subjectPrecursor B-Cell Lymphoblastic Leukemia-Lymphoma
dc.subjectCell Transdifferentiation
dc.subjectPrecursor Cells, B-Lymphoid
dc.subjectInduced Pluripotent Stem Cells
dc.subjectTranscriptome
dc.subjectHeterografts
dc.subjectCellular Reprogramming
dc.subjectBiomarkers
dc.titleDevelopment Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency.
dc.typeJournal Article
dcterms.dateAccepted2016-08-23
rioxxterms.versionofrecord10.1016/j.stemcr.2016.08.013
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2016-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfStem cell reports
pubs.issue4
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublished
pubs.volume7
pubs.embargo.termsNo embargo
icr.researchteamBiology of Childhood Leukaemiaen_US
dc.contributor.icrauthorFord, Anthonyen


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