Nfe2l3 (Nrf3) deficiency predisposes mice to T-cell lymphoblastic lymphoma

Blood. 2011 Feb 10;117(6):2005-8. doi: 10.1182/blood-2010-02-271460. Epub 2010 Dec 8.


We have previously generated mice deficient for Nfe213 (NF-E2 p45 related factor 3 or Nrf3), a member of the cap 'n' collar family of basic-leucine zipper transcription factors. To examine whether Nrf3 is involved in chemical-induced carcinogenesis, we exposed the mice to benzo[a]pyrene (B[a]P), a carcinogen found in cigarette smoke. Contrary to wild-type mice, Nrf3-null animals are highly susceptible to B[a]P, exhibiting significantly increased mortality. Pathology analysis of affected tissue sections revealed a high incidence of T-cell lymphoblastic lymphoma in B[a]P-treated Nrf3(-/-) mice. Lymphoblastic lymphoma occasionally metastasized into the lung as demonstrated by perivascular malignant lymphocytic infiltration. Together, our studies show that the absence of Nrf3 predisposes mice to lymphoma development, suggesting a protective role of this transcription factor in hematopoietic malignancies. Our data demonstrate the first in vivo function of Nrf3 and its link to tumor development. Nrf3-deficient mice may serve as a preclinical mouse model to study carcinogen-induced lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / deficiency*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Benzo(a)pyrene / toxicity
  • Disease Models, Animal
  • Disease Susceptibility
  • Humans
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Knockout
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / etiology*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology


  • Basic-Leucine Zipper Transcription Factors
  • NFE2L3 protein, human
  • Nrf3 protein, mouse
  • Benzo(a)pyrene