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IL-6 and MYC collaborate in plasma cell tumor formation in mice. Blood 2010 Mar 04;115(9):1746-54

Date

12/19/2009

Pubmed ID

20018915

Pubmed Central ID

PMC2832814

DOI

10.1182/blood-2009-08-237941

Abstract

Interleukin-6 (IL-6) plays a critical role in the natural history of human plasma cell neoplasms (PCNs), such as plasma cell myeloma and plasmacytoma (PCT). IL-6 is also at the center of neoplastic plasma cell transformation in BALB/c (C) mice carrying a transgene, H2-L(d)-IL6, that encodes human IL-6 under control of the major histocompatibility complex H2-L(d) promoter: strain C.H2-L(d)-IL6. These mice are prone to PCT, but tumor development is incomplete with long latencies ( approximately 40% PCT at 12 months of age). To generate a more robust mouse model of IL-6-dependent PCN, we intercrossed strain C.H2-L(d)-IL6 with strains C.iMyc(Emu) or C.iMyc(Calpha), 2 interrelated gene-insertion models of the chromosomal T(12;15) translocation causing deregulated expression of Myc in mouse PCT. Deregulation of MYC is also a prominent feature of human PCN. We found that double-transgenic C.H2-L(d)-IL6/iMyc(Emu) and C.H2-L(d)-IL6/iMyc(Calpha) mice develop PCT with full penetrance (100% tumor incidence) and short latencies (3-6 months). The mouse tumors mimic molecular hallmarks of their human tumor counterparts, including elevated IL-6/Stat3/Bcl-X(L) signaling. The newly developed mouse strains may provide a good preclinical research tool for the design and testing of new approaches to target IL-6 in treatment and prevention of human PCNs.

Author List

Rutsch S, Neppalli VT, Shin DM, DuBois W, Morse HC 3rd, Goldschmidt H, 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
Antibodies, Monoclonal
Disease Models, Animal
Gene Expression Profiling
Genes, myc
Humans
Hyperplasia
Interleukin-6
Mice
Mice, Transgenic
Neoplasm Transplantation
Plasma Cells
Plasmacytoma
Signal Transduction
Translocation, Genetic
jenkins-FCD Prod-406 0f9a74600e4e79798f8fa6f545ea115f3dd948b2