DEVELOPMENTAL REGULATION OF ALPHA-1,3-FUCOSYL-TRANSFERASE EXPRESSION IN CD34 POSITIVE PROGENITORS AND MATURING MYELOID CELLS ISOLATED FROM NORMAL HUMAN BONE-MARROW

The adhesive interactions of hemopoietic cells within the bone marrow regulate their distribution, growth, and development, Fucosylated stru ctures, of which sialyl Lewis x has been most extensively studied, are important ligands for selectins, but little is known about their func tion or regulation during normal hemopoietic development. We have stud ied alpha 1,3-fucosyltransferase activity in CD34 positive progenitors and myeloid cells at different stages of maturation isolated form nor mal human bone marrow, together with mRNA levels of Fuc-TIV and Fuc-TV II. Enzyme activity measured with H type 2 acceptor was present at all stages but was markedly elevated in fractions of early myeloid cells enriched for promyelocytes, correlating with the appearance of Lewis x on these cells, and thereafter fell progressively as cells matured, A ctivity measured with 3'sialyllactosamine was present in CD34+ cells a nd at all stages of maturation. Levels were low in promyelocyte/myeloc yte transitional cells and increased, relative to those measured with H type 2, during the later stages of maturation; these changes correla te directly with a maturation-related increase in sialyl Lewis x expre ssion, Using competitive quantitative RT-PCR, mRNA levels of Fuc-TIV a nd Fuc-TVII were similar in CD34+ cells, early myeloid and late myeloi d cells. The significance of these findings in relation to fucosyltran sferase activity, the synthesis of selectin ligands and differences be tween normal cells and leukemic cell lines is discussed.