IL-6 and MYC collaborate in plasma cell tumor formation in mice

Sebastian Rutsch; Vishala T Neppalli; Dong-Mi Shin; Wendy DuBois; Herbert C Morse III; Hartmut Goldschmidt; Siegfried Janz

doi:10.1182/blood-2009-08-237941

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IL-6 and MYC collaborate in plasma cell tumor formation in mice

Journal article

Open access

Peer reviewed

IL-6 and MYC collaborate in plasma cell tumor formation in mice

Sebastian Rutsch, Vishala T Neppalli, Dong-Mi Shin, Wendy DuBois, Herbert C Morse III, Hartmut Goldschmidt and Siegfried Janz

Blood, Vol.115(9), pp.1746-1754

03/04/2010

DOI: 10.1182/blood-2009-08-237941

PMCID: PMC2832814

PMID: 20018915

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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.

Signal Transduction

Hyperplasia

Neoplasm Transplantation

Translocation, Genetic

Interleukin-6 - genetics

Antibodies, Monoclonal - biosynthesis

Humans

Plasmacytoma - genetics

Mice, Transgenic

Plasmacytoma - immunology

Gene Expression Profiling

Plasmacytoma - pathology

Genes, myc

Plasma Cells - pathology

Animals

Mice

Plasmacytoma - etiology

Disease Models, Animal

Details

Title: Subtitle: IL-6 and MYC collaborate in plasma cell tumor formation in mice
Creators: Sebastian Rutsch - Medizinische Klinik V, University of Heidelberg, and National Center for Tumor Diseases, Heidelberg, Germany
Vishala T Neppalli
Dong-Mi Shin
Wendy DuBois
Herbert C Morse III
Hartmut Goldschmidt
Siegfried Janz
Resource Type: Journal article
Publication Details: Blood, Vol.115(9), pp.1746-1754
DOI: 10.1182/blood-2009-08-237941
PMID: 20018915
PMCID: PMC2832814
ISSN: 0006-4971
eISSN: 1528-0020
Grant note: Intramural NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS P50CA097274 / NCI NIH HHS
Language: English
Date published: 03/04/2010
Academic Unit: Pathology
Record Identifier: 9984083834502771

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