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 language | English |
|---|---|
| Pages (from-to) | 349-360 |
| Number of pages | 12 |
| Journal | Cancer Cell |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 10 2007 |
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Keywords
- CELLCYCLE
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis
AU - Carrasco, Daniel R.
AU - Sukhdeo, Kumar
AU - Protopopova, Marina
AU - Sinha, Raktim
AU - Enos, Miriam
AU - Carrasco, Daniel E
AU - Zheng, Mei
AU - Mani, Mala
AU - Henderson, Joel
AU - Pinkus, Geraldine S.
AU - Munshi, Nikhil
AU - Horner, James
AU - Ivanova, Elena V.
AU - Protopopov, Alexei
AU - Anderson, Kenneth C.
AU - Tonon, Giovanni
AU - DePinho, Ronald A.
PY - 2007/4/10
Y1 - 2007/4/10
N2 - 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.
AB - 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.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=34047136169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047136169&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2007.02.015
DO - 10.1016/j.ccr.2007.02.015
M3 - Article
C2 - 17418411
AN - SCOPUS:34047136169
VL - 11
SP - 349
EP - 360
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 4
ER -