LYMPHOID NEOPLASIA Brief report Nfe2l3 (Nrf3) deficiency predisposes mice to T-cell lymphoblastic lymphoma

We have previously generated mice defi-cient for Nfe213 (NF-E2 p45 related factor 3 or Nrf3), a member of the cap ‘n ’ collar family of basic-leucine zipper transcrip-tion factors. To examine whether Nrf3 is involved in chemical-induced carcinogen-esis, 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 suscep-tible to B[a]P, exhibiting significantly in-creased mortality. Pathology analysis of affected tissue sections revealed a high incidence of T-cell lymphoblastic lym-phoma in B[a]P-treated Nrf3/mice. Lym-phoblastic lymphoma occasionally metas-tasized into the lung as demonstrated by perivascular malignant lymphocytic infil-tration. 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 pre-clinical mouse model to study carcinogen-induced lymphomagenesis. (Blood. 2011; 117(6):2005-2008