Figure 1. Accumulation of ceramides following targeting of SphK2 within PEL cells.

A. The core pathways of sphingolipid metabolism. B.–C. BCBL-1 cells were incubated with the indicated concentrations of ABC294640 (ABC) or vehicle for 16 h, then ceramide and dihydro (dh)-ceramide species were quantified as described in Methods. D. NOD/SCID mice were injected i.p. with 10⁷ BCBL-1 cells. Beginning 21 days later, mice were administered 100 mg/kg ABC or vehicle (n = 10 per group) i.p. once daily, five days per week, for another 21 days. Live PEL cell lysates were recovered from ascites fractions from each of 3 representative vehicle- or drug-treated mice, and intracellular ceramide and dh-ceramide species quantified as above. Error bars represent the S.E.M. for 2 independent experiments, * = p < 0.05; ** = P < 0.01. E.–F. Relative proportions of specific ceramide and dh-ceramide species within vehicle- or drug-treated PEL cells from in vitro E. and in vivo F. experiments are presented.