Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma.

Holly A.F. Stessman, Aatif Mansoor, Fenghuang Zhan, Michael A. Linden, Brian Van Ness, Linda Baughn

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Multiple myeloma (MM), the second most common hematopoietic malignancy, remains an incurable plasma cell (PC) neoplasm. While the proteasome inhibitor, bortezomib (Bz) has increased patient survival, resistance represents a major treatment obstacle as most patients ultimately relapse becoming refractory to additional Bz therapy. Current tests fail to detect emerging resistance; by the time patients acquire resistance, their prognosis is often poor. To establish immunophenotypic signatures that predict Bz sensitivity, we utilized Bz-sensitive and -resistant cell lines derived from tumors of the Bcl-X(L)/Myc mouse model of PC malignancy. We identified significantly reduced expression of two markers (CD93, CD69) in "acquired" (Bz-selected) resistant cells. Using this phenotypic signature, we isolated a subpopulation of cells from a drug-naïve, Bz-sensitive culture that displayed "innate" resistance to Bz. Although these genes were identified as biomarkers, they may indicate a mechanism for Bz-resistance through the loss of PC maturation which may be induced and/or selected by Bz. Significantly, induction of PC maturation in both "acquired" and "innate" resistant cells restored Bz sensitivity suggesting a novel therapeutic approach for reversing Bz resistance in refractory MM.

Original languageEnglish (US)
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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myeloma
plasma cells
Plasma Cells
Multiple Myeloma
Plasmas
mice
therapeutics
neoplasms
relapse
proteasome endopeptidase complex
cells
resistance mechanisms
prognosis
biomarkers
animal models
cell lines
Refractory materials
drugs
Plasma Cell Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma. / Stessman, Holly A.F.; Mansoor, Aatif; Zhan, Fenghuang; Linden, Michael A.; Van Ness, Brian; Baughn, Linda.

In: PLoS One, Vol. 8, No. 10, 01.01.2013.

Research output: Contribution to journalArticle

Stessman, Holly A.F. ; Mansoor, Aatif ; Zhan, Fenghuang ; Linden, Michael A. ; Van Ness, Brian ; Baughn, Linda. / Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma. In: PLoS One. 2013 ; Vol. 8, No. 10.
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