Generation of a novel, multi-stage, progressive, and transplantable model of plasma cell neoplasms Journal Article


Authors: Asai, T.; Hatlen, M. A.; Lossos, C.; Ndiaye-Lobry, D.; Deblasio, A.; Murata, K.; Fleisher, M.; Cortizas, E. M.; Verdun, R. E.; Petrini, J.; Nimer, S. D.
Article Title: Generation of a novel, multi-stage, progressive, and transplantable model of plasma cell neoplasms
Abstract: Multiple myeloma is a plasma cell neoplasm with an extremely variable clinical course. Animal models are needed to better understand its pathophysiology and for preclinical testing of potential therapeutic agents. Hematopoietic cells expressing the hypermorphic Rad50 s allele show hematopoietic failure, which can be mitigated by the lack of a transcription factor, Mef/Elf4. However, we find that 70% of Mef-/-Rad50s/s mice die from multiple myeloma or other plasma cell neoplasms. These mice initially show an abnormal plasma cell proliferation and monoclonal protein production, and then develop anemia and a decreased bone mineral density. Tumor cells can be serially transplanted and according to array CGH and whole exome sequencing, the pathogenesis of plasma cell neoplasms in these mice is not linked to activation of a specific oncogene, or inactivation of a specific tumor suppressor. This model recapitulates the systemic manifestations of human plasma cell neoplasms, and implicates cooperativity between the Rad50s and Mef/Elf4 pathways in initiating myelomagenic mutations that promote plasma cell transformation.
Journal Title: Scientific Reports
Volume: 6
ISSN: 2045-2322
Publisher: Nature Publishing Group  
Date Published: 2016-03-10
Start Page: 22760
Language: English
DOI: 10.1038/srep22760
PROVIDER: scopus
PMCID: PMC4785351
PUBMED: 26961797
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
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MSK Authors
  1. John Petrini
    76 Petrini
  2. Kazunori Murata
    12 Murata
  3. Martin Fleisher
    237 Fleisher
  4. Megan A Hatlen
    14 Hatlen