Plasmacytomagenesis in Eμ-v-abl transgenic mice is accelerated when apoptosis is restrained.
Publication Year 2014-07-01, Volume 124, Issue #7, Page 1099-1109
- Journal Title
- Publication Type
- JOURNAL ARTICLE
- Mice susceptible to plasma cell tumors provide a useful model for human multiple myeloma. We have shown previously that mice expressing an Eμ-v-abl oncogene develop solely plasmacytomas. Here we show here that loss of the pro-apoptotic BH3-only protein Bim or, to a lesser extent, over-expression of anti-apoptotic Bcl-2 or Mcl-1, significantly accelerated the development of plasmacytomas and increased their incidence. Disease was preceded by an increased abundance of plasma cells, presumably reflecting their enhanced survival capacity in vivo. Plasmacytomas of each genotype expressed high levels of v-abl and frequently harboured a rearranged c-myc gene, probably as a result of chromosome translocation. As in human multiple myelomas, elevated expression of cyclin D genes was common and p53 deregulation rare. Our results for plasmacytomas highlight the significance of anti-apoptotic changes in multiple myeloma, which include elevated expression of Mcl-1 and, less frequently, Bcl-2, and suggest that closer attention to defects in Bim expression is warranted.
- American Society for Hematology
- WEHI Research Division(s)
- Molecular Genetics Of Cancer
- Link To PubMed Central Version
- Publisher's Version
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Creation Date: 2014-07-30 02:50:03Last Modified: 0001-01-01 12:00:00