Plasma cell tumour progression in iMyc gene-insertion mice

J. S. Kim, S. S. Han, S. S. Park, N. McNeil, S. Janz

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The authors have recently reported that gene-targeted iMyc mice that carry a His6-tagged mouse Myc cDNA, MycHis, just 5′ of the immunoglobulin heavy-chain enhancer, Eμ, are prone to 'spontaneous' neoplasms of the B-lymphocyte lineage. The present study has used histological, immunohistochemical, and molecular genetic methods to investigate a subset of these neoplasms referred to as extraosseous plasmacytomas (PCTs). It is shown that 20.8% (20/96) of tumour-bearing iMyc mice on a mixed genetic background of segregating C57BL/6 and 129/SvJ alleles develop PCT by 500 days. The MycHis-induced PCTs produced monoclonal immunoglobulin and developed in the gut-associated lymphoid tissue (GALT), particularly the mesenteric node and Peyer's patches. The PCTs overexpressed MycHis, at the expense of normal Myc, and exhibited gene expression changes on cDNA macroarrays that were consistent with MycHis-driven neoplasia. Surprisingly, in one of three PCT-derived cell lines, MycHis was 'replaced' by a naturally occurring T(12;15) translocation, which changed the mode of Myc deregulation from gene insertion (MycHis transgene) to chromosomal translocation (juxtaposition of normal Myc to the immunoglobulin heavy-chain locus Igh). These findings provide evidence that recreation of the mouse PCT-associated T(12;15)(Igh-Myc) translocation by gene insertion in mice results in the predictable development of PCTs in approximately one-fifth of the tumour-bearing mice. MycHis-driven PCTs recapitulate aspects of human plasma cell neoplasms, for which relatively few models exist in mice. For example, PCT development in the iMyc mice may provide a good system to study the mechanism by which human MYC facilitates the progression of plasma cell myeloma (multiple myeloma) in humans.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalJournal of Pathology
Issue number1
StatePublished - May 2006

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine


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