To that end, dual blockade of AC and GCS in MDR leukemia models resulted in profound increases in cellular ceramide levels that were accompanied by apoptotic cell death involving inactivation of Akt, GSK-3β activation, and increases in the Bcl-2 family member Mcl-1S, the pro-apoptotic splice variant of anti-apoptotic Mcl-1L, and decisive declines in mitochondrial respiratory kinetics. The gene discussed is BCL2; the disease is leukemia.