Document Detail


Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation.
MedLine Citation:
PMID:  20679395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Verena Labi; Miriam Erlacher; Gerhard Krumschnabel; Claudia Manzl; Alexandar Tzankov; Josephina Pinon; Alexander Egle; Andreas Villunger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  24     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-03     Completed Date:  2010-08-17     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1602-7     Citation Subset:  IM    
Affiliation:
Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck 6020, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis* / genetics
Apoptosis Regulatory Proteins / genetics,  metabolism
Cell Proliferation
DNA Damage* / radiation effects
DNA Replication
Gamma Rays
Hematopoietic Stem Cells / cytology,  radiation effects
Leukocytes / pathology*,  radiation effects
Lymphoma / genetics,  physiopathology*
Mice
Mice, Knockout
T-Lymphocytes / cytology,  physiology
Tumor Suppressor Protein p53 / metabolism
Tumor Suppressor Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/PUMA protein, mouse; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins
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