@article{Jérôme Moreaux_Dirk Hose_Michel Jourdan_Thierry Reme_Michael Hundemer_Marion Moos_Nicolas Robert_Philippe Moine_John De Vos_Hartmut Goldschmidt_Bernard Klein_2007, place={Pavia, Italy}, title={TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines}, volume={92}, url={https://haematologica.org/article/view/4474}, DOI={10.3324/haematol.10574}, abstractNote={<strong>Background and Objectives</strong> 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. <em>TACI</em> 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<sup>high</sup> MM cells resemble bone marrow plasma cells and TACI<sup>low</sup> resemble plasmablasts. The aim of this study was to further characterize the role of TACI expression in MM<strong>Design and Methods</strong> Using gene expression profiling, we investigated whether these patterns are kept in TACI<sup>+</sup> or TACI<sup>−</sup> HMCL.<strong>Results</strong> Eighty genes/EST interrogated by Affymetrix microarrays were differentially expressed between TACI<sup>+</sup> and TACI<sup>−</sup> HMCL, particularly c-maf, cyclin D2, and integrin β7. Triggered by the finding that TACI and <em>c-maf</em> expressions correlate in TACI<sup>+</sup> HMCL, we demonstrated that TACI activation influences <em>c-maf</em> expression: (i) activation of TACI by BAFF or APRIL increases <em>c-maf</em>, <em>cyclin D2</em>, and <em>integrin</em> β<em>7</em> gene expressions in TACI<sup>+</sup> HMCL, (ii) blocking of autocrine BAFF/APRIL stimulation in some TACI<sup>+</sup> HMCL by the TACI-Fc fusion protein reduces <em>c-maf</em>, <em>cyclin D2</em>, and <em>integrin</em> β<em>7</em> gene expression, (iii) nucleofection of siRNA to <em>c-maf</em> decreases <em>c-maf</em> mRNA levels and reduces the expression of <em>cyclin D2</em> and integrin β7 gene expressions, without affecting TACI expression<strong>Interpretation and Conclusions</strong> We conclude that TACI activation can upregulate <em>c-maf</em> expression which, in turn, controls <em>cyclin D2</em>, and <em>integrin</em> β<em>7</em&gt; gene expression.}, number={6}, journal={Haematologica}, author={Jérôme Moreaux and Dirk Hose and Michel Jourdan and Thierry Reme and Michael Hundemer and Marion Moos and Nicolas Robert and Philippe Moine and John De Vos and Hartmut Goldschmidt and Bernard Klein}, year={2007}, month={Jun.}, pages={803-811} }