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IL-6 transgenic mouse model for extraosseous plasmacytoma

  1. Author:
    Kovalchuk, A. L.
    Kim, J. S.
    Park, S. S.
    Coleman, A. E.
    Ward, J. M.
    Morse, H. C.
    Kishimoto, T.
    Potter, M.
    Janz, S.

  2. Author Address

    NCI, Genet Lab, Canc Res Ctr, NIH, Bldg 37, Room 2B10, Bethesda, MD 20892 USA. NCI, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Korea Res Inst Biosci & Biotechnol, Taejon 305333, South Korea. NCI, Vet & Tumor Pathol Sect, NIH, Ft Detrick, MD 21702 USA. Osaka Univ, Sch Med, Inst Mol & Cellular Biol, Osaka 565, Japan. Janz S NCI, Genet Lab, Canc Res Ctr, NIH, Bldg 37, Room 2B10, Bethesda, MD 20892 USA.
    1. Year: 2002
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 99
    2. 3
    3. Pages: 1509-1514
  4. Type of Article: Article
  1. 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, approximate to30% 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.

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