C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity

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  • dc.contributor.author Rapino, Francesca, 1982-
  • dc.contributor.author Robles, Eloy F.
  • dc.contributor.author Richter-Larrea, Jose A.
  • dc.contributor.author Kallin, Eric M.
  • dc.contributor.author Martinez-Climent, Jose A.
  • dc.contributor.author Graf, T. (Thomas)
  • dc.date.accessioned 2024-12-03T07:36:01Z
  • dc.date.available 2024-12-03T07:36:01Z
  • dc.date.issued 2013
  • dc.description.abstract Earlier work demonstrated that the transcription factor C/EBPα can convert immature and mature murine B lineage cells into functional macrophages. Testing >20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPαER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/EBPα was inactivated, a hallmark of cell reprogramming. Interestingly, C/EBPα induction also impaired the cells’ tumorigenicity. Likewise, C/EBPα efficiently converted a lymphoblastic leukemia B cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced by C/EBPα to transdifferentiate into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy for treating B cell malignancies.
  • dc.description.sponsorship We would like to thank Dr. E.R. Stanley for hrCSF-1, Dr. N. Dean for mCherry-labeled C. albicans, Dr. R. Copin for dsRed-labeled E. coli, A. Ferrer and M. Hummel for microarray services, Gustavo Mostoslavsky for the Phage2 TetOP and rtTA puromycin plasmids, E. Ciordia for animal care, and I. Peñuelas for assistance with microPET. We acknowledge funding from the Ministerio de Educación y Ciencia, SAF.2007-63058, AGAUR 2009 SGR 768, and EU-FP7 project BLUEPRINT (282510) to T.G., and the Ministerio de Salud ISCIII (FIS-PI12/0202 and RTICC-RD12/0036/0063-FEDER) and the French-Spanish CITTIL project to J.A.M.-C. F.R. is funded by La Caixa International PhD Fellowship.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Rapino F, Robles EF, Richter-Larrea JA, Kallin EM, Martinez-Climent JA, Graf T. C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity. Cell Reports. 2013 Apr;3(4):1153-63. DOI: 10.1016/j.celrep.2013.03.003
  • dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2013.03.003
  • dc.identifier.issn 2211-1247
  • dc.identifier.uri http://hdl.handle.net/10230/68898
  • dc.language.iso eng
  • dc.publisher Cell Press
  • dc.relation.ispartof Cell Reports. 2013 Apr;3(4):1153-63
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
  • dc.rights This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.other Limfomes
  • dc.subject.other Leucèmia
  • dc.subject.other Tumors
  • dc.title C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion