Novel targeted deregulation of c-Myc cooperates with Bcl-XL to cause plasma cell neoplasms in mice

Wan Cheung Cheung; Joong Su Kim; Michael Linden; Liangping Peng; Brian Van Ness; Roberto D Polakiewicz; Siegfried Janz

doi:10.1172/JCI200420369

Back

Novel targeted deregulation of c-Myc cooperates with Bcl-XL to cause plasma cell neoplasms in mice

Journal article

Open access

Peer reviewed

Novel targeted deregulation of c-Myc cooperates with Bcl-XL to cause plasma cell neoplasms in mice

Wan Cheung Cheung, Joong Su Kim, Michael Linden, Liangping Peng, Brian Van Ness, Roberto D Polakiewicz and Siegfried Janz

The Journal of clinical investigation, Vol.113(12), pp.1763-1773

06/15/2004

DOI: 10.1172/JCI200420369

PMCID: PMC420503

PMID: 15199411

Files and links (1)

url

https://doi.org/10.1172/JCI200420369View

Published (Version of record) Open Access

Abstract

Deregulated expression of both Myc and Bcl-X L are consistent features of human plasma cell neoplasms (PCNs). To investigate whether targeted expression of Myc and Bcl-X L in mouse plasma cells might lead to an improved model of human PCN, we generated Myc transgenics by inserting a single-copy histidine-tagged mouse Myc gene, Myc His , into the mouse Ig heavy-chain Cα locus. We also generated Bcl-X L transgenic mice that contain a multicopy Flag-tagged mouse Bcl-x Flag transgene driven by the mouse Ig κ light-chain 3′ enhancer. Single-transgenic Bcl-X L mice remained tumor free by 380 days of age, whereas single-transgenic Myc mice developed B cell tumors infrequently (4 of 43, 9.3%). In contrast, double-transgenic Myc/Bcl-X L mice developed plasma cell tumors with short onset (135 days on average) and full penetrance (100% tumor incidence). These tumors produced monoclonal Ig, infiltrated the bone marrow, and contained elevated amounts of Myc His and Bcl-X L Flag proteins compared with the plasma cells that accumulated in large numbers in young tumor-free Myc/Bcl-X L mice. Our findings demonstrate that the enforced expression of Myc and Bcl-X L by Ig enhancers with peak activity in plasma cells generates a mouse model of human PCN that recapitulates some features of human multiple myeloma.

Details

Title: Subtitle: Novel targeted deregulation of c-Myc cooperates with Bcl-XL to cause plasma cell neoplasms in mice
Creators: Wan Cheung Cheung - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Joong Su Kim - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Michael Linden - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Liangping Peng - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Brian Van Ness - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Roberto D Polakiewicz - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Siegfried Janz - Cell Signaling Technology Inc., Beverly, Massachusetts, USA
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.113(12), pp.1763-1773
DOI: 10.1172/JCI200420369
PMID: 15199411
PMCID: PMC420503
NLM abbreviation: J Clin Invest
ISSN: 0021-9738
eISSN: 1558-8238
Publisher: American Society for Clinical Investigation
Language: English
Date published: 06/15/2004
Academic Unit: Pathology
Record Identifier: 9984083893102771

Metrics

12 Record Views

97 Times Cited - Web of Science