The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis
Carrasco, Daniel R.
Ivanova, Elena V.
Carrasco, Daniel E.
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CitationCarrasco, Daniel R., Kumar Sukhdeo, Marina Protopopova, Raktim Sinha, Miriam Enos, Daniel E. Carrasco, Mei Zheng, et al. 2007. The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis. Cancer Cell 11(4): 349-360.
AbstractMultiple 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8160855
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