IL-6 transgenic mouse model for extraosseous plasmacytoma.
Plasma cell neoplasms in humans comprise plasma cell myeloma, otherwise known as multiple myeloma, Ig deposition and heavy chain diseases, and plasmacytoma (PCT). A subset of PCT, designated extramedullary PCT, is distinguished from multiple myeloma and solitary PCT of bone by its distribution among various tissue sites but not the bone marrow. Extramedullary (extraosseus) PCT are rare spontaneous neoplasms of mice but are readily induced in a susceptible strain, BALB/c, by treatment with pristane. The tumors develop in peritoneal granulomas and are characterized by Myc-activating T(12;15) chromosomal translocations and, most frequently, by secretion of IgA. A uniting feature of human and mouse plasma cell neoplasms is the critical role played by IL-6, a B cell growth, differentiation, and survival factor. To directly test the contribution of IL-6 to PCT development, we generated BALB/c mice carrying a widely expressed IL-6 transgene. All mice exhibited lymphoproliferation and plasmacytosis. By 18 months of age, over half developed readily transplantable PCT in lymph nodes, Peyer's patches, and sometimes spleen. These neoplasms also had T(12;15) translocations, but remarkably, none expressed IgA. Unexpectedly, approximately 30% of the mice developed follicular and diffuse large cell B cell lymphomas that often coexisted with PCT. These findings provide a unique model of extramedullary PCT for studies on pathogenesis and treatment and suggest a previously unappreciated role for IL-6 in the genesis of germinal center-derived lymphomas.
Kovalchuk
Alexander L
AL
Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kim
Joong Su
JS
Park
Sung Sup
SS
Coleman
Allen E
AE
Ward
Jerrold M
JM
Morse
Herbert C
HC
Kishimoto
Tadamitsu
T
Potter
Michael
M
Janz
Siegfried
S
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D016259:Genes, myc; D006099:Granuloma / Q000276:immunology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation / Q000276:immunology; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014178:Translocation, Genetic
D015850:Interleukin-6