The genetic regulation of fucosylated and sialylated antigens on developing myeloid cells

Abstract

The first part of this article reviews the stages of normal development of haemopoietic cells committed to the myeloid lineage, properties of leukaemic cell lines that are arrested at specific maturation stages along the granulocytic pathway, the structures of carbohydrate antigenic markers that appear on myeloid cell surfaces, with especial reference to sialyl-Le(x) (NeuAcalpha2-3Galbeta1-4[Fucalpha1-3]GlcNAc), and the role of this antigen on mature granulocytes as a ligand for selectin molecules. The families of fucosyl- and sialyltransferase genes encoding enzymes responsible for the biosynthesis of sialyl-Le(x), and the pathways leading to the formation of this antigen, and more complex related structures, are described. The second part of the article outlines the work carried out in the authors' laboratory with leukaemic cell lines in an attempt to ascertain the biochemical and genetic basis of the lowering of sialyl-Le(x) expression that occurs at intermediate stages of normal haemopoietic development. Analysis of enzyme levels and mRNA expression of the fucosyl- and sialyltransferase genes has led to the conclusion that depletion of substrate resulting from high levels of enzyme activity from co-expressed genes FUT4 and ST6Gal1 probably accounts for the dip in expression of sialyl-Le(x), rather than a change in the level of expression of FUT7, the gene in myeloid cells encoding the enzyme ultimately responsible for the synthesis of sialyl-Le(x). The possible significance of this change in relation to normal cell maturation is discussed.