REGULATION OF GLYCOLIPID SYNTHESIS IN HL-60 CELLS BY ANTISENSE OLIGODEOXYNUCLEOTIDES TO GLYCOSYLTRANSFERASE SEQUENCES - EFFECT ON CELLULAR-DIFFERENTIATION

Treatment of the human promyelocytic leukemia cell line HL-60 with ant isense oligodeoxynucleotides to UDP-N-acetylgalactosamine:beta-1,4-N-a cetyl transferase (GM2-synthase; EC 2.4.1.92) and CMP-sialic acid:alph a-2,8-sialyltransferase (GD3-synthase; EC 2.4.99.8) sequences effectiv ely dean-regulated the synthesis of more complex gangliosides in the g anglioside synthetic pathways after GM3, resulting in a remarkable inc rease in endogenous GM3 with concomitant decreases in more complex gan gliosides, The treated cells underwent monocytic differentiation as ju dged by morphological changes, adherent ability, and nitroblue tetrazo lium staining, These data provide evidence that the increased endogeno us ganglioside GM3 may play an important role in regulating cellular d ifferentiation and that the antisense DNA technique proves to be a pow erful tool in manipulating glycolipid synthesis in the cell.