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TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines.

Abstract : BACKGROUND AND OBJECTIVES: BAFF and APRIL stimulate the growth of multiple myeloma (MM) cells. BAFF and APRIL share two receptors--TACI and BCMA--and BAFF binds to a third receptor, BAFF-R. We previously reported that TACI gene expression is bimodal in 18 human MM cell lines (HMCL), being either present or absent, unlike BCMA that is expressed on all HMCL. BAFF-R is lacking. TACI expression is a good indicator of a BAFF-binding receptor in HMCL. In primary MM cells, the level of TACI expression correlates with a characteristic phenotypic pattern: TACIhighMM cells resemble bone marrow plasma cells and TACIlow resemble plasmablasts. The aim of this study was to further characterize the role of TACI expression in MM DESIGN AND METHODS: Using gene expression profiling, we investigated whether these patterns are kept in TACI+ or TACI- HMCL. RESULTS: Eighty genes/EST interrogated by Affymetrix microarrays were differentially expressed between TACI+ and TACI- HMCL, particularly c-maf, cyclin D2, and integrin beta7. Triggered by the finding that TACI and c-maf expressions correlate in TACI+ HMCL, we demonstrated that TACI activation influences c-maf expression: (i) activation of TACI by BAFF or APRIL increases c-maf, cyclin D2, and integrin beta7 gene expressions in TACI+ HMCL, (ii) blocking of autocrine BAFF/APRIL stimulation in some TACI+ HMCL by the TACI-Fc fusion protein reduces c-maf, cyclin D2, and integrin beta7 gene expression, (iii) nucleofection of siRNA to c-maf decreases c-maf mRNA levels and reduces the expression of cyclin D2 and integrin beta7 gene expressions, without affecting TACI expression INTERPRETATION AND CONCLUSIONS: We conclude that TACI activation can upregulate c-maf expression which, in turn, controls cyclin D2, and integrin beta7 gene expression.
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https://www.hal.inserm.fr/inserm-00162002
Contributor : Monique Frei <>
Submitted on : Tuesday, November 10, 2009 - 4:32:51 PM
Last modification on : Friday, May 15, 2020 - 12:22:03 PM
Long-term archiving on: : Thursday, April 8, 2010 - 11:03:15 PM

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  • HAL Id : inserm-00162002, version 1
  • PUBMED : 17550853

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Jérôme Moreaux, Dirk Hose, Michel Jourdan, Thierry Rème, Michael Hundemer, et al.. TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines.. Haematologica, Ferrata Storti Foundation, 2007, 92 (6), pp.803-11. ⟨inserm-00162002⟩

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