Rituximab-induced early and late signaling have opposite effects on dexamethasone-induced apoptosis in human follicular lymphoma cells.

The addition of rituximab (RTX) to standard chemotherapy has improved the treatment of B-cell malignancies. We show here that RTX and dexamethasone (Dex) induced synergistic apoptosis in follicular lymphoma cell lines. However, apoptosis was delayed by RTX-induced early protective signaling. RTX-induced early signaling also decreased Dex-induced apoptosis and led to phosphorylation of ERK1/2, Bcl-2 (at serine 70) and phosphorylation/degradation of BimL/EL. All these events were prevented by the MEK inhibitor, UO126. Therefore, we suggest that RTX-induced ERK-mediated signaling events lead to protection from apoptosis during early signaling and that blocking of Bim and Bcl-2 phosphorylation might be used as a novel strategy for lymphoma treatment.