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Series GSE6980 Query DataSets for GSE6980
Status Public on Apr 09, 2007
Title The Differentiation and Stress Response Factor, XBP-1, Drives Multiple Myeloma Pathogenesis
Organism Mus musculus
Experiment type Expression profiling by array
Summary Multiple myeloma (MM) evolves from highly prevalent premalignant condition termed Monoclonal Gammopathy of Undetermined Significance (MGUS). We report an MGUS-MM phenotype arising in transgenic mice with Emu-directed expression of the unfolded protein/ER stress response and plasma cell development spliced isoform factor XBP-1s. Emu-XBP-1s elicited elevated serum Ig and IL-6 levels, skin alterations and with advancing age, a significant proportion of Emu-xbp-1s transgenic mice develop features diagnostic of human MM including bone lytic lesions. Transcriptional profiles of Emu-xbp-1s B lymphoid and MM cells show aberrant expression of genes known to be dysregulated in human MM including Cyclin D1, MAF, MAFB, and APRIL. This genetic model coupled with documented frequent XBP-1s overexpression in human MM serve to implicate chronic XBP-1s dysregulation in the development of this common and lethal malignancy.
Keywords: XBP-1, MGUS, multiple myeloma, transgenic mouse
 
Overall design In this study, we have explored the biological impact of sustained XBP-1s expression in the lymphoid system, anticipating that this genetic event would be a necessary component along with other MM-relevant oncogenes and tumor suppressor gene manipulations to generate a MM-prone mouse model. Unexpectedly, XBP-1s overexpression alone yielded an MGUS-MM disease bearing many features classical of the human disease on the clinical, pathological and molecular levels.
We performed expression analysis of B cells derived from the spleen of 20-week old Emu-xbp-1s mice (n=5) and non-transgenic mice (n=5). Additionally, we analyzed the expression profiles from MM tumor cells arising in Emu-xbp-1s mice (n=6).
 
Contributor(s) 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
Citation(s) 17418411
Submission date Feb 07, 2007
Last update date Feb 11, 2019
Contact name Ronald A DePinho
E-mail(s) ron_depinho@dfci.harvard.edu, giovanni_tonon@dfci.harvard.edu, ruben_carrasco@dfci.harvard.edu
Organization name Dana Farber Cancer Institute
Street address 44 Binney St. M417
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (16)
GSM160730 WildType B cells Spleen 1
GSM160731 Wild Type B cells Spleen 2
GSM160739 Wild Type B cells Spleen 3
Relations
BioProject PRJNA99289

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Supplementary file Size Download File type/resource
GSE6980_RAW.tar 68.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file

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