“…Thus, abnormal sphingolipid catabolism or accumulation in lipid microdomains might result in a cell autonomous defect accounting for GLD hematopoietic stem cells compromised functionality (i.e., proliferation, migration, and maturation). Furthermore, because psychosine directly deregulates some specific protein kinase C isozymes (Hannun and Bell, 1987), activates phospholipase A2 (Giri et al, 2006), and modifies mitochondrial membrane potential (Tapasi, 1998) and peroxisomal activity (Khan et al, 2005), its accumulation within thymic stromal tissue or in T cells might also directly interfere with cell survival. Of note, a recent study reported that psychosine favors proinflammatory cytokine secretion by peripheral blood mononuclear cells derived from Krabbe patients (Formichi et al, 2007;Pasqui et al, 2007).…”