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

doi:10.1016/j.ccr.2007.02.015

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

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	349-360
Number of pages	12
Journal	Cancer Cell
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2007.02.015
Publication status	Published - Apr 10 2007

Keywords

CELLCYCLE

ASJC Scopus subject areas

Cancer Research
Cell Biology
Oncology

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10.1016/j.ccr.2007.02.015

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Carrasco, D. R., Sukhdeo, K., Protopopova, M., Sinha, R., Enos, M., Carrasco, DE., Zheng, M., Mani, M., Henderson, J., Pinkus, G. S., Munshi, N., Horner, J., Ivanova, E. V., Protopopov, A., Anderson, K. C., Tonon, G., & 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 journal › Article › peer-review

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, 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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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.",

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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.

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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.

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

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Keywords

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