AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center Malignancies

Marta Chesi, Davide F. Robbiani, Michael Sebag, Wee Joo Chng, Maurizio Affer, Rodger Tiedemann, Riccardo Valdez, Stephen E. Palmer, Stephanie S. Haas, A. Keith Stewart, Rafael Fonseca, Richard Kremer, Giorgio Cattoretti, P. Leif Bergsagel

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

By misdirecting the activity of Activation-Induced Deaminase (AID) to a conditional MYC transgene, we have achieved sporadic, AID-dependent MYC activation in germinal center B cells of Vk*MYC mice. Whereas control C57BL/6 mice develop benign monoclonal gammopathy with age, all Vk*MYC mice progress to an indolent multiple myeloma associated with the biological and clinical features highly characteristic of the human disease. Furthermore, antigen-dependent myeloma could be induced by immunization with a T-dependent antigen. Consistent with these findings in mice, more frequent MYC rearrangements, elevated levels of MYC mRNA, and MYC target genes distinguish human patients with multiple myeloma from individuals with monoclonal gammopathy, implicating a causal role for MYC in the progression of monoclonal gammopathy to multiple myeloma.

Original languageEnglish (US)
Pages (from-to)167-180
Number of pages14
JournalCancer cell
Volume13
Issue number2
DOIs
StatePublished - Feb 5 2008

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Chesi, M., Robbiani, D. F., Sebag, M., Chng, W. J., Affer, M., Tiedemann, R., Valdez, R., Palmer, S. E., Haas, S. S., Stewart, A. K., Fonseca, R., Kremer, R., Cattoretti, G., & Bergsagel, P. L. (2008). AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center Malignancies. Cancer cell, 13(2), 167-180. https://doi.org/10.1016/j.ccr.2008.01.007