title: Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells.
abstract: 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.
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Fehniger
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Ponnappan
authors.forename: J B
authors.initials: JB
authors.lastname: VanDeusen
authors.forename: M A
authors.initials: MA
authors.lastname: Cooper
authors.forename: S M
authors.initials: SM
authors.lastname: Florea
authors.forename: A G
authors.initials: AG
authors.lastname: Freud
authors.forename: M L
authors.initials: ML
authors.lastname: Robinson
authors.forename: J
authors.initials: J
authors.lastname: Durbin
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: 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
chemical_list: D017931:DNA Primers; D018836:Inflammation Mediators; D019409:Interleukin-15