BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone Export

@article{citeulike:5983355, abstract = {Identification of growth factors in neoplasias may be a target for future therapies by blocking either growth factor receptor interaction or the induced pathway. Using gene expression profiling, we identified overexpression of 2 receptors for a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) in malignant plasma cells compared with normal plasma cells. APRIL and BAFF are involved in a variety of tumor and autoimmune diseases, including B-cell malignancies. We confirmed the expression of BAFF and APRIL receptors (B-cell maturation antigen [BCMA], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and BAFF-R) in a majority of 13 myeloma cell lines and in the purified primary myeloma cells of 11 patients. APRIL and BAFF were potent survival factors for exogenous cytokine-dependent myeloma cell lines and were autocrine growth factors for the RPMI8226 and L363 autonomously growing cell lines. These factors activated nuclear factor (NF)-{kappa}B, phosphatidylinositol-3 (PI-3) kinase/AKT, and mitogen-activated protein kinase (MAPK) kinase pathways and induced a strong up-regulation of the Mcl-1 and Bcl-2 antiapoptotic proteins in myeloma cells. BAFF or APRIL was also involved in the survival of primary myeloma cells cultured with their bone-marrow environment, and protected them from dexamethasone (DEX)-induced apoptosis. Finally, the serum levels of BAFF and APRIL were increased about 5-fold in patients with multiple myeloma (MM) as compared with healthy donors. Altogether, these data suggest that APRIL/BAFF inhibitors may be of clinical value in MM. (Blood. 2004;103:3148-3157) 10.1182/blood-2003-06-1984}, author = {Moreaux, Jerome and Legouffe, Eric and Jourdan, Eric and Quittet, Philippe and Reme, Thierry and Lugagne, Cecile and Moine, Philippe and Rossi, Jean-Francois and Klein, Bernard and Tarte, Karin}, citeulike-article-id = {5983355}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2003-06-1984}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/content/103/8/3148.abstract}, citeulike-linkout-2 = {http://bloodjournal.hematologylibrary.org/content/103/8/3148.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15070697}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15070697}, comment = {10,22,09 }, day = {15}, doi = {10.1182/blood-2003-06-1984}, issn = {0006-4971}, journal = {Blood}, keywords = {april, hspg}, month = {April}, number = {8}, pages = {3148--3157}, posted-at = {2009-10-22 01:46:56}, priority = {0}, title = {BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone}, url = {http://dx.doi.org/10.1182/blood-2003-06-1984}, volume = {103}, year = {2004} }

TY - JOUR ID - citeulike:5983355 L3 - citeulike-article-id:5983355 N2 - Identification of growth factors in neoplasias may be a target for future therapies by blocking either growth factor receptor interaction or the induced pathway. Using gene expression profiling, we identified overexpression of 2 receptors for a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) in malignant plasma cells compared with normal plasma cells. APRIL and BAFF are involved in a variety of tumor and autoimmune diseases, including B-cell malignancies. We confirmed the expression of BAFF and APRIL receptors (B-cell maturation antigen [BCMA], transmembrane activator and calcium modulator and cyclophilin ligand interactor [TACI], and BAFF-R) in a majority of 13 myeloma cell lines and in the purified primary myeloma cells of 11 patients. APRIL and BAFF were potent survival factors for exogenous cytokine-dependent myeloma cell lines and were autocrine growth factors for the RPMI8226 and L363 autonomously growing cell lines. These factors activated nuclear factor (NF)-{kappa}B, phosphatidylinositol-3 (PI-3) kinase/AKT, and mitogen-activated protein kinase (MAPK) kinase pathways and induced a strong up-regulation of the Mcl-1 and Bcl-2 antiapoptotic proteins in myeloma cells. BAFF or APRIL was also involved in the survival of primary myeloma cells cultured with their bone-marrow environment, and protected them from dexamethasone (DEX)-induced apoptosis. Finally, the serum levels of BAFF and APRIL were increased about 5-fold in patients with multiple myeloma (MM) as compared with healthy donors. Altogether, these data suggest that APRIL/BAFF inhibitors may be of clinical value in MM. (Blood. 2004;103:3148-3157) 10.1182/blood-2003-06-1984 IS - 8 JF - Blood SN - 0006-4971 EP - 3157 TI - BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone VL - 103 SP - 3148 KW - april KW - hspg N1 - 10,22,09 AU - Moreaux, Jerome AU - Legouffe, Eric AU - Jourdan, Eric AU - Quittet, Philippe AU - Reme, Thierry AU - Lugagne, Cecile AU - Moine, Philippe AU - Rossi, Jean-Francois AU - Klein, Bernard AU - Tarte, Karin PY - 2004/04/15/ UR - http://dx.doi.org/10.1182/blood-2003-06-1984 ER -