Labi 2010 Genes Dev
|Labi V, Erlacher M, Krumschnabel G, Manzl C, Tzankov A, Pinon J, Egle A, Villunger A (2010) Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation. Genes Dev 24:1602-07.|
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.
• Keywords: p53, BH3-only proteins, Stem cells, g-irradiation, Cancer
Labels: Pathology: Cancer Stress:Cell death