The Journal of Experimental Medicine
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Published online 15 January 2001.
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© The Rockefeller University Press, 0022-1007/2001/1/219/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 2, January 15, 2001 219-232


Original Article

Fatal Leukemia in Interleukin 15 Transgenic Mice Follows Early Expansions in Natural Killer and Memory Phenotype Cd8+ T Cells

Todd A. Fehnigera,b, Kazuhiro Suzukia,c, Anand Ponnappana, Jeffrey B. VanDeusena,b, Megan A. Coopera,b, Sorin M. Floreaa, Aharon G. Freuda, Michael L. Robinsond, Joan Durbind, and Michael A. Caligiuria,b

a Department of Internal Medicine, Division of Hematology/Oncology, Columbus, Ohio 43210
b Department of Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210
c Department of Urology, Gunma University School of Medicine, Gunma 371-8511, Japan
d Children's Hospital and Research Institute, Columbus, Ohio 43205
The Ohio State University, 458A Starling-Loving Hall, 320 West 10th Ave., Columbus, OH 43210.614-293-7522614-293-7521

caligiuri-1{at}medctr.osu.edu

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.

Key Words: interleukin 15 • leukemia • transgenic mice • lymphocytes • inflammation


Abbreviations used in this paper: hGH, human growth hormone; IL-15tg, IL-15 transgenic; LGL, large granular lymphocytic; RT, reverse transcription.

T.A. Fehniger and K. Suzuki contributed equally to this work.

© 2001 The Rockefeller University Press


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