Faculty Collaboration Database

IL-6 transgenic mouse model for extraosseous plasmacytoma. Proc Natl Acad Sci U S A 2002 Feb 05;99(3):1509-14

Date

01/24/2002

Pubmed ID

11805288

Pubmed Central ID

PMC122221

DOI

10.1073/pnas.022643999

Scopus ID

2-s2.0-0037022341 (requires institutional sign-in at Scopus site)   113 Citations

Abstract

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.

Author List

Kovalchuk AL, Kim JS, Park SS, Coleman AE, Ward JM, Morse HC 3rd, Kishimoto T, Potter M, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Cell Division
Cell Survival
Chromosome Mapping
Disease Models, Animal
Genes, myc
Granuloma
Humans
In Situ Hybridization, Fluorescence
Interleukin-6
Lymphoma, B-Cell
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Transplantation
Plasmacytoma
Time Factors
Translocation, Genetic