Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells

Todd A. Fehniger, Kazuhiro Suzuki, Anand Ponnappan, Jeffrey B. VanDeusen, Megan A. Cooper, Sorin M. Florea, Aharon G. Freud, Michael L. Robinson, Joan Durbin, Michael A. Caligiuri

Research output: Contribution to journalArticlepeer-review

290 Scopus citations

Abstract

Inflammation likely has a role in the early genesis of certain malignancies. Interleukin (IL)-15, a proinflammatory cytokine and growth factor, is required for lymphocyte homeostasis. Intriguingly, the expression of IL-15 protein is tightly controlled by multiple posttranscriptional mechanisms. Here, we engineered a transgenic mouse to overexpress IL-15 by eliminating these posttranscriptional checkpoints. IL-15 transgenic mice have early expansions in natural killer (NK) and CD8+ T lymphocytes. Later, these mice develop fatal lymphocytic leukemia with a T-NK phenotype. These data provide novel evidence that leukemia, like certain other cancers, can arise as the result of chronic stimulation by a proinflammatory cytokine.

Original languageEnglish (US)
Pages (from-to)219-231
Number of pages13
JournalJournal of Experimental Medicine
Volume193
Issue number2
DOIs
StatePublished - Jan 15 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Inflammation
  • Interleukin 15
  • Leukemia
  • Lymphocytes
  • Transgenic mice

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