title: C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity.
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.
authors.affiliation: Center for Genomic Regulation, Universidad Pompeu Fabra and Institució Catalana de Recerca i Estudis Avançats, Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rapino
authors.forename: Eloy F
authors.initials: EF
authors.lastname: Robles
authors.forename: Jose A
authors.initials: JA
authors.lastname: Richter-Larrea
authors.forename: Eric M
authors.initials: EM
authors.lastname: Kallin
authors.forename: Jose A
authors.initials: JA
authors.lastname: Martinez-Climent
authors.forename: Thomas
authors.initials: T
authors.lastname: Graf
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use / Q000633:toxicity; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D045744:Cell Line, Tumor; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis; D013629:Tamoxifen / Q000627:therapeutic use / Q000633:toxicity; D059467:Transcriptome; D014183:Transplantation, Heterologous
chemical_list: D018931:Antineoplastic Agents, Hormonal; D022763:CCAAT-Enhancer-Binding Protein-alpha; D013629:Tamoxifen