1. Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation.
- Author
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Labi, Verena, Erlacher, Miriam, Krumschnabel, Gerhard, Manzl, Claudia, Tzankov, Alexandar, Pinon, Josephina, Egle, Alexander, and Villunger, Andreas
- Subjects
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APOPTOSIS , *DNA damage , *CARCINOGENESIS , *IRRADIATION , *TUMORS - 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 γ-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. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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