Involvement of macroautophagy in the caspase-independent killing of Burkitt lymphoma cell lines by rituximab

摘要

The encouraging clinical impact of rituximab (RTX) upon the treatment of many B-cell lymphoproliferative disorders, including non-Hodgkin lymphoma, is well-documented, although the exact mechanism(s) by which this chimeric anti-CD20 monoclonal antibody eliminates B-cells remains unknown. Studies suggest the involvement of antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and classical, caspase-dependent apoptosis (Smith, 2003). More recently we (Daniels et al, 2006), and others (Chan et al, 2003) have found that in addition to these systems, RTX can also kill B-cells via a novel, caspase-independent cell death pathway (CI-CD). Using Burkitt Lymphoma (BL) cell lines as a model of human disease, RTX-induced CI-CD was shown to be characterised by phosphatidylserine exposure, mitochondrial depolarisation, nuclear enlargement, cytoplasmic vacuolisation (Daniels et al, 2006) and a chronic rise in intracellular calcium (Daniels et al, 2008). A complete understanding of the mechanismsof this pathway could have important clinical implications for the treatment of chemo-refractive malignancies in which the classical, caspase-dependent pathway is disabled