B-Cell Receptor-Mediated Glucosylceramide Synthesis Protects Primary CLL Cells From Ceramide-Dependent Apoptosis

Abstract 1766 Introduction: Survival of CLL cells is triggered by the B-cell receptor (BCR). However, little is known about metabolic processes, which are influenced by the BCR and which are essential for survival of malignant cells such as sphingolipid metabolism. Certain sphingolipids are considered as bioeffector signaling molecules since they regulate several pathways involved in cell metabolism and survival (e.g. mitochondria). For instance ceramide, as the central molecule in sphingolipid metabolism, contributes to apoptosis and growth inhibition. In contrast, glucosylceramide, generated out of ceramide, is responsible for proliferative attributes such as resistance to apoptosis and to several chemotherapeutics. We therefore investigated the role of sphingolipid metabolism in survival and apoptosis-resistance of CLL cells. Methods and Results: We performed liquid chromatography electrospray ionization tandem mass spectrometry of 8 CLL samples in order to determine sphingolipid levels. Prior analysis, cells were either incubated with anti-IgM immunobeads for 24h or were left native. IgM stimulation significantly increased survival of primary CLL cells (n=9; p=0.0246) shown by flow cytometry. Our mass spectrometric analysis revealed a significant decrease of apoptosis-inducing ceramide in BCR-stimulated CLL cells compared to native controls (16:0 p C.M.W. and L.P.F contributed equally to this work. Disclosures: No relevant conflicts of interest to declare.