IL-6 transgenic mouse model for extraosseous plasmacytoma

Alexander L Kovalchuk; Siegfried Janz; Joong Su Kim; Sung Sup Park; Allen E Coleman; Jerrold M Ward; Herbert C Morse III; Tadamitsu Kishimoto; Michael Potter

doi:10.1073/pnas.022643999

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IL-6 transgenic mouse model for extraosseous plasmacytoma

Journal article

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Peer reviewed

IL-6 transgenic mouse model for extraosseous plasmacytoma

Alexander L Kovalchuk, Siegfried Janz, Joong Su Kim, Sung Sup Park, Allen E Coleman, Jerrold M Ward, Herbert C Morse III, Tadamitsu Kishimoto and Michael Potter

Proceedings of the National Academy of Sciences - PNAS, Vol.99(3), pp.1509-1514

02/05/2002

DOI: 10.1073/pnas.022643999

PMCID: PMC122221

PMID: 11805288

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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.

Cell Differentiation

Translocation, Genetic

Interleukin-6 - genetics

Cell Survival

Humans

Mice, Inbred C57BL

Plasmacytoma - genetics

In Situ Hybridization, Fluorescence

Mice, Transgenic

Neoplasm Transplantation - immunology

Plasmacytoma - immunology

Chromosome Mapping

Plasmacytoma - pathology

Genes, myc

Animals

Time Factors

Cell Division

Interleukin-6 - immunology

Lymphoma, B-Cell - immunology

Lymphoma, B-Cell - pathology

Granuloma - immunology

Mice

Disease Models, Animal

Details

Title: Subtitle: IL-6 transgenic mouse model for extraosseous plasmacytoma
Creators: Alexander L Kovalchuk - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Siegfried Janz
Joong Su Kim
Sung Sup Park
Allen E Coleman
Jerrold M Ward
Herbert C Morse III
Tadamitsu Kishimoto
Michael Potter
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.99(3), pp.1509-1514
DOI: 10.1073/pnas.022643999
PMID: 11805288
PMCID: PMC122221
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 02/05/2002
Academic Unit: Pathology
Record Identifier: 9984083231602771

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