The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis

Daniel R. Carrasco, Kumar Sukhdeo, Marina Protopopova, Raktim Sinha, Miriam Enos, Daniel E Carrasco, Mei Zheng, Mala Mani, Joel Henderson, Geraldine S. Pinkus, Nikhil Munshi, James Horner, Elena V. Ivanova, Alexei Protopopov, Kenneth C. Anderson, Giovanni Tonon, Ronald A. DePinho

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.

Original languageEnglish
Pages (from-to)349-360
Number of pages12
JournalCancer Cell
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 10 2007

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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