FADD and acute lymphoblastic leukemia: Here we report (1) that ceramide synthase-6 (CERS6), an enzyme responsible for the generation of C16 ceramides, is overexpressed in T-cell ALL cells compared with T lymphocytes and PBMCs; (2) that genetic modification of CERS6 in T-cell ALL cell lines resulted in significant changes in sensitivity to chemotherapeutic drugs; and (3) that CERS6 binds to Fas and renders resistance to chemotherapy via the extrinsic apoptotic pathway by interfering with the Fas–FADD association in ALL cells.