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
• Publication Date: 2002-07-26T16:48:33Z
• Authors: 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
• Keywords: Interleukin-15; 0303 health sciences; Leukemia, Experimental; Time Factors; Base Sequence; Mice, Transgenic; Lymphocytosis; CD8-Positive T-Lymphocytes; 3. Good health; Killer Cells, Natural; Mice; 03 medical and health sciences; Phenotype; Animals; Inflammation Mediators; Genetic Engineering; Immunologic Memory; DNA Primers

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.