Ceramides and glycosphingolipids in maturation process: leukemic cells as an experimental model

Leukemic cells were used as experimental material to demonstrate changes in the content of GSLs during the development and maturation of neutrophils. The most abundant cellular GSL is LacCer. An elevation in the LacCer level occurs twice during the maturation process: initially, on formation of azurophil granules, and subsequently, (a more significant rise) on formation of specific granules. The formation of the latter is accompanied by an increase in the level of GalGalCer. During the maturation of myeloblasts, there is a simultaneous growth in the content of LacCer and GM3 as well as that of their common precursors, that is, free ceramides. Like other tumor cells, GM3 rich myeloblasts in the peripheral blood from patients with AML are characterized by shedding of gangliosides. The quantitative Cer/GlcCer ratio in these cells seems to be advantageous for the efficacy of chemotherapy in the induction of apoptosis. Myelo- and metamyelocytes achieve the highest level of GSLs. Their entry into the full maturity stage is accompanied by a decrease in the level of GSLs. Patterns of GSLs expression change greatly during development and maturation. However, with respect to the composition and content of GSLs, there are no significant differences between normal and leukemic mature neutrophils. At each stage of the development and maturation of myelogenous leukemic cells, as well as in normal mature neutrophils, there occurs the synthesis of the same molecular species both free ceramides and ceramide portions of LacCer, precursor of more complex GSLs.