BCR-mediated chemoresistance differs from CD40L and IL-4 by regulating ceramides and glucosylceramides levels. LC-ESI-MS/MS was applied to determine sphingolipid levels in CLL cells from 8 patients. (A) After stimulation with anti-IgM immunobeads, IL-4, and CD40L for 24 hours, a reduction of apoptotic ceramide levels could be observed (IgM, P = .0258; IL-4, P = .0478; CD40L, P = .0114). (B) Pro-survival glucosylceramide was exclusively increased after BCR engagement (P = .0435). Data are mean ± SEM of the sums of all analyzed fatty acyl subspecies per analyzed sample of 8 independent experiments. Statistics are calculated by paired t test.