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Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation

Labi, Verena and Erlacher, Miriam and Krumschnabel, Gerhard and Manzl, Claudia and Tzankov, Alexandar and Pinon, Josephina and Egle, Alexander and Villunger, Andreas. (2010) Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation. Genes & development, Vol. 24, H. 15. pp. 1602-1607.

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Official URL: http://edoc.unibas.ch/dok/A6003305

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Abstract

Apoptosis triggered by p53 upon DNA damage secures removal of cells with compromised genomes, and is thought to prevent tumorigenesis. In contrast, we provide evidence that p53-induced apoptosis can actively drive tumor formation. Mice defective in p53-induced apoptosis due to loss of its proapoptotic target gene, puma, resist gamma-irradiation (IR)-induced lymphomagenesis. In wild-type animals, repeated irradiation injury-induced expansion of hematopoietic stem/progenitor cells (HSCs) leads to lymphoma formation. Puma(-/-) HSCs, protected from IR-induced cell death, show reduced compensatory proliferation and replication stress-associated DNA damage, and fail to form thymic lymphomas, demonstrating that the maintenance of stem/progenitor cell homeostasis is critical to prevent IR-induced tumorigenesis.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
UniBasel Contributors:Tzankov, Alexandar
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cold Spring Harbor Laboratory
ISSN:0890-9369
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:25

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