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

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Deregulated expression of both Myc and Bcl-XL are consistent features of human plasma cell neoplasms (PCNs). To investigate whether targeted expression of Myc and Bcl-XL 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, MycHis, into the mouse Ig heavy-chain Cα locus. We also generated Bcl-XL transgenic mice that contain a multicopy Flag-tagged mouse Bcl-xFlag transgene driven by the mouse Ig κ light-chain 3′ enhancer. Single-transgenic Bcl-XL 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-XL 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 MycHis and Bcl-XL Flag proteins compared with the plasma cells that accumulated in large numbers in young tumor-free Myc/Bcl-XL mice. Our findings demonstrate that the enforced expression of Myc and Bcl-XL by Ig enhancers with peak activity in plasma cells generates a mouse model of human PCN that recapitulates some features of human multiple myeloma.

Original languageEnglish (US)
Pages (from-to)1763-1773
Number of pages11
JournalJournal of Clinical Investigation
Volume113
Issue number12
DOIs
StatePublished - Jun 2004

Fingerprint

Dive into the research topics of 'Novel targeted deregulation of c-Myc cooperates with Bcl-X<sub>L</sub> to cause plasma cell neoplasms in mice'. Together they form a unique fingerprint.

Cite this