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

Inflammation likely has a role in the early genesis of certain malignancies . Interleukin (IL)-15, a proinflammatory cytokine and growth factor, is req uired for lymphocyte homeostasis. Intriguingly, the expression of IL-15 pro tein is tightly controlled by multiple posttranscriptional mechanisms. Here , we engineered a transgenic mouse to overexpress IL-15 by eliminating thes e posttranscriptional checkpoints. IL-15 transgenic mice have early expansi ons in natural killer (NK) and CD8(+) T lymphocytes. Later, these mice deve lop fatal lymphocytic leukemia with a T-NK phenotype. These data provide no vel evidence that leukemia, like certain other cancers, can arise as the re sult of chronic stimulation by a proinflammatory cytokine.