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 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.
Fehniger
T A
TA
Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Suzuki
K
K
Ponnappan
A
A
VanDeusen
J B
JB
Cooper
M A
MA
Florea
S M
SM
Freud
A G
AG
Robinson
M L
ML
Durbin
J
J
Caligiuri
M A
MA
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D005818:Genetic Engineering; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology*; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D008218:Lymphocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D013997:Time Factors
D017931:DNA Primers; D018836:Inflammation Mediators; D019409:Interleukin-15