Improvement of the rituximab–induced cell death by potentiation of the store-operated calcium entry in mantle cell lymphoma cell lines

Mantle Cell Lymphoma (MCL) is one of the worst lymphomas with a median overall survival of 3 to 4 years. Even if the use of rituximab was a great step in therapy, patients commonly develop resistance and relapse. New therapies or complement of existing therapies should be developed. Using spectrofluorimetry, we found that the resting cytosolic Ca(2+) ion concentration [Ca(2+)](cyt) of MCL patients cells and MCL cell lines was increased. This increase is correlated with a larger store-operated calcium entry (SOCE) amplitude which is responsible for the Ca(2+) ions influx. Furthermore, using a SOCE potentiating agent, we demonstrated that in the MCL Rec-1 cell line, the SOCE is already activated in resting conditions. Interestingly, this potentiating agent alone, by disturbing the SOCE, induced the apoptosis of Rec-1 cells with the same efficacy than rituximab. The use of the potentiating agent in addition to rituximab strengthens the rituximab-induced apoptosis of rituximab-sensitive Granta-519 and Rec-1 cells. However, this potentiating agent cannot convert the Jeko-1 rituximab-resistant to a rituximab-sensitive cell line. Our results confirm that the use of compound acting on the Ca(2+) homeostasis could be a new target of interest in complement to existing therapies.