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IL-6 transgenic mouse model for extraosseous plasmacytoma
Alexander L Kovalchuk1, Joong Su Kim, Sung Sup Park
1Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Summary
Interleukin-6 (IL-6) overexpression in mice induced extramedullary plasmacytoma (PCT) and lymphomas. This study provides a novel model for studying these plasma cell neoplasms and highlights IL-6
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Plasma cell neoplasms include multiple myeloma and plasmacytoma (PCT).
- Extramedullary PCT occurs outside bone marrow and is rare in mice but inducible.
- Interleukin-6 (IL-6) is crucial for B cell development and implicated in plasma cell neoplasms.
Purpose of the Study:
- To investigate the direct role of IL-6 in the development of extramedullary PCT.
- To establish a mouse model for studying PCT pathogenesis and treatment.
Main Methods:
- Generated BALB/c mice with a widely expressed IL-6 transgene.
- Monitored mice for lymphoproliferation, plasmacytosis, and tumor development.
- Characterized tumor genetics, including chromosomal translocations and IgA expression.
Main Results:
- IL-6 transgene expression led to lymphoproliferation and plasmacytosis in all mice.
- Over half of the mice developed transplantable extramedullary PCT by 18 months.
- PCTs exhibited T(12;15) translocations but lacked IgA expression.
- Approximately 30% of mice developed B cell lymphomas, often coexisting with PCT.
Conclusions:
- Widely expressed IL-6 drives the development of extramedullary PCT in mice.
- IL-6 plays a significant role in the pathogenesis of germinal center-derived lymphomas.
- These findings establish a valuable mouse model for extramedullary PCT research.