Journal Article

DKFZ-2017-03925

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cell competition is a tumour suppressor mechanism in the thymus.

Martins, V. C. (First author)DKFZ* ; Busch, K.DKFZ* ; Juraeva, D.DKFZ* ; Blum, C. ; Ludwig, C. ; Rasche, V. ; Lasitschka, F. ; Mastitsky, S. E.DKFZ* ; Brors, B.DKFZ* ; Hielscher, T.DKFZ* ; Fehling, H. J.DKFZ* ; Rodewald, H.-R. (Last author)DKFZ*

2014
Nature Publ. Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/nature13317

Abstract: Cell competition is an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors. Here we show that in mice this turnover is regulated by natural cell competition between young bone-marrow-derived and old thymus-resident progenitors that, although genetically identical, execute differential gene expression programs. Disruption of cell competition leads to progenitor self-renewal, upregulation of Hmga1, transformation, and T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease in pathology, genomic lesions, leukaemia-associated transcripts, and activating mutations in Notch1. Hence, cell competition is a tumour suppressor mechanism in the thymus. Failure to select fit progenitors through cell competition may explain leukaemia in X-linked severe combined immune deficiency patients who showed thymus-autonomous T-cell development after therapy with gene-corrected autologous progenitors.

Keyword(s): HMGA Proteins ; Notch1 protein, mouse ; Receptor, Notch1

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Contributing Institute(s):

1. Zelluläre Immunologie (D110)
2. Theoretische Bioinformatik (B080)
3. Biostatistik (C060)
4. Angewandte Bioinformatik (G200)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF >= 30 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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