HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moreaux, J. Articles by Klein, B. Search for Related Content PubMed PubMed Citation Articles by Moreaux, J. Articles by Klein, B.

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

From the CHU Montpellier, Institute of Research in Biotherapy, Montpellier, F-34285 France (JM, MJ, NR, PM, JDV, BK); Université Montpellier1, F-34967 France (JDV, BK); INSERM, U847, Montpellier, F-34197 France (JM, MJ, TR, JDV, BK); Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, INF410, 69120 Heidelberg, Germany (DH, MH, MM, HG)

Correspondence: Bernard Klein, INSERM U475, 99, rue Puech Villa, 34197 Montpellier Cedex 5, France. E-mail: klein{at}montp.inserm.fr

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: TACI^high MM cells resemble bone marrow plasma cells and TACI^low 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 ß7. 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 ß7 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 ß7 gene expression, (iii) nucleofection of siRNA to c-maf decreases c-maf mRNA levels and reduces the expression of cyclin D2 and integrin ß7 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 ß7 gene expression.

Key words: myeloma, TACI, gene expression profiles, c-maf.