IL-6 transgenic mouse model for extraosseous plasmacytoma.

in Proceedings of the National Academy of Sciences of the United States of America by Alexander L Kovalchuk, Joong Su Kim, Sung Sup Park, Allen E Coleman, Jerrold M Ward, Herbert C Morse, Tadamitsu Kishimoto, Michael Potter, Siegfried Janz

TLDR

  • The study found that mice with an IL-6 transgene developed PCT and lymphomas, with approximately 30% of the mice developing follicular and diffuse large cell B cell lymphomas. This suggests that IL-6 plays a critical role in the development of these diseases.

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.

Overview

  • The study focuses on plasma cell neoplasms in humans, specifically extramedullary PCT, and their development in mice. The hypothesis being tested is the role of IL-6 in PCT development and its potential contribution to the genesis of germinal center-derived lymphomas. The methodology used involves generating BALB/c mice carrying a widely expressed IL-6 transgene and observing their lymphoproliferation and plasmacytosis. The primary objective of the study is to investigate the role of IL-6 in PCT development and its potential impact on the genesis of germinal center-derived lymphomas.

Comparative Analysis & Findings

  • The study compares the outcomes observed in mice with and without the IL-6 transgene. The results show that all mice with the IL-6 transgene exhibited lymphoproliferation and plasmacytosis. By 18 months of age, over half of the mice 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. The key findings of the study suggest a previously unappreciated role for IL-6 in the genesis of germinal center-derived lymphomas.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The unique model of extramedullary PCT provides a valuable opportunity for studies on pathogenesis and treatment. The study also highlights the previously unappreciated role for IL-6 in the genesis of germinal center-derived lymphomas. Future research directions could include further investigation of the mechanisms underlying the development of PCT and lymphomas in mice with the IL-6 transgene, as well as the potential for IL-6 as a therapeutic target for these diseases.
Read Full Article