Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation

Genes Dev. 2010 Aug 1;24(15):1602-7. doi: 10.1101/gad.1940210.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis* / genetics
  • Cell Proliferation
  • DNA Damage* / radiation effects
  • DNA Replication
  • Gamma Rays
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / radiation effects
  • Leukocytes / pathology*
  • Leukocytes / radiation effects
  • Lymphoma / genetics
  • Lymphoma / physiopathology*
  • Mice
  • Mice, Knockout
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism


  • Apoptosis Regulatory Proteins
  • PUMA protein, mouse
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins