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 journalArticle

263 Citations (Scopus)

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

Fingerprint

Multiple Myeloma
Protein Isoforms
Protein Unfolding
Heat-Shock Proteins
Plasma Cells
Transgenic Mice
Phenotype
Bone and Bones
Skin
Serum
Genes

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Carrasco, D. R., Sukhdeo, K., Protopopova, M., Sinha, R., Enos, M., Carrasco, DE., ... DePinho, R. A. (2007). The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis. Cancer Cell, 11(4), 349-360. https://doi.org/10.1016/j.ccr.2007.02.015

The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis. / Carrasco, Daniel R.; Sukhdeo, Kumar; Protopopova, Marina; Sinha, Raktim; Enos, Miriam; Carrasco, Daniel E; Zheng, Mei; Mani, Mala; Henderson, Joel; Pinkus, Geraldine S.; Munshi, Nikhil; Horner, James; Ivanova, Elena V.; Protopopov, Alexei; Anderson, Kenneth C.; Tonon, Giovanni; DePinho, Ronald A.

In: Cancer Cell, Vol. 11, No. 4, 10.04.2007, p. 349-360.

Research output: Contribution to journalArticle

Carrasco, DR, Sukhdeo, K, Protopopova, M, Sinha, R, Enos, M, Carrasco, DE, Zheng, M, Mani, M, Henderson, J, Pinkus, GS, Munshi, N, Horner, J, Ivanova, EV, Protopopov, A, Anderson, KC, Tonon, G & DePinho, RA 2007, 'The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis', Cancer Cell, vol. 11, no. 4, pp. 349-360. https://doi.org/10.1016/j.ccr.2007.02.015
Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE et al. The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis. Cancer Cell. 2007 Apr 10;11(4):349-360. https://doi.org/10.1016/j.ccr.2007.02.015
Carrasco, Daniel R. ; Sukhdeo, Kumar ; Protopopova, Marina ; Sinha, Raktim ; Enos, Miriam ; Carrasco, Daniel E ; Zheng, Mei ; Mani, Mala ; Henderson, Joel ; Pinkus, Geraldine S. ; Munshi, Nikhil ; Horner, James ; Ivanova, Elena V. ; Protopopov, Alexei ; Anderson, Kenneth C. ; Tonon, Giovanni ; DePinho, Ronald A. / The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis. In: Cancer Cell. 2007 ; Vol. 11, No. 4. pp. 349-360.
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