Targeting protein kinase C in mantle cell lymphoma

摘要: Although targeting the Bruton tyrosine kinase (BTK) with ibrutinib has changed lymphoma treatment, patients mantle cell (MCL) remain incurable. In this study, we characterized a broad range of MCL lines and primary cells respect to response BTK inhibitor, ibrutinib, compared it protein C (PKC) sotrastaurin. At clinically relevant concentrations, each drug induced potent death only in REC-1 line, which was accompanied by robust inhibition AKT ERK1/ERK2 (ERK1/2, also termed MAPK3/MAPK1) phosphorylation. sensitive cells, drug-mediated impaired phosphorylation obvious on levels B-cell receptor-induced basal Similar results were obtained subset The various drug-resistant showed very distinct responses terms ERK1/2 Interestingly, PKC at same time led ibrutinib-mediated rescue weak sotrastaurin-induced apoptosis MINO cells. Additional sensitized inhibitor-mediated cytotoxicity. summary, are heterogeneous their or inhibition, indicating need for even more individualized targeted treatment approaches subsets patients.