Fatal Leukemia in Interleukin 15 Transgenic Mice Follows Early Expansions in Natural Killer and Memory Phenotype CD8+ T Cells

doi:10.1084/jem.193.2.219

Published online 16 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. Fehniger^a,b, Kazuhiro Suzuki^a,c, Anand Ponnappan^a, Jeffrey B. VanDeusen^a,b, Megan A. Cooper^a,b, Sorin M. Florea^a, Aharon G. Freud^a, Michael L. Robinson^d, Joan Durbin^d, and Michael A. Caligiuri^a,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

Correspondence to: Michael A. Caligiuri, The Ohio State University, 458A Starling-Loving Hall, 320 West 10th Ave., Columbus, OH 43210. Tel:614-293-7521 Fax:614-293-7522 E-mail:caligiuri-1{at}medctr.osu.edu.

Inflammation likely has a role in the early genesis of certainmalignancies. Interleukin (IL)-15, a proinflammatory cytokineand growth factor, is required for lymphocyte homeostasis. Intriguingly,the expression of IL-15 protein is tightly controlled by multipleposttranscriptional mechanisms. Here, we engineered a transgenicmouse to overexpress IL-15 by eliminating these posttranscriptionalcheckpoints. IL-15 transgenic mice have early expansions innatural killer (NK) and CD8⁺ T lymphocytes. Later, these micedevelop fatal lymphocytic leukemia with a T-NK phenotype. Thesedata provide novel evidence that leukemia, like certain othercancers, can arise as the result of chronic stimulation by aproinflammatory cytokine.

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

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