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Enzymic control of the expression of the X determinant (CD15) in human
myeloid cells during maturation: the regulatory role of 6- sialytransferase
PO Skacel, AJ Edwards, CT Harrison and WM Watkins
Division of Immunochemical Genetics and MRC Clinical Research Centre,
Middlesex, UK.
To establish the basis for the reduced expression of the X determinant on
leukemic blasts and the changes in antigenic expression that occur during
myeloid maturation, the presence on myeloid cells of X and related
structures was examined in conjunction with studies on the activities of
the glycosyltransferases involved in their biosynthesis. Expression of X
and sialyl-X was weak on blasts in comparison with neutrophils despite the
presence of the requisite precursor structures. Much higher levels of
3-fucosyltransferase activity were found in blasts than in neutrophils when
nonsialylated substrates were used, but, whereas the enzyme in neutrophils
reacted equally well with 3'- sialylated and nonsialylated acceptors, the
enzyme in blasts showed a marked preference for nonsialylated substrates.
6'-Sialyltransferase activity was strong in blasts but was not detectable
in neutrophils, whereas a much lower level of 3'-sialyltransferase activity
was present in both blasts and neutrophils. Dimethyl sulfoxide-induced
maturation of HL60 cells was associated with (1) a decrease in both 6'-
sialyltransferase and 3-fucosyltransferase activities, (2) a change in the
substrate specificity of 3-fucosyltransferase towards that found in mature
cells, and (3) increased cell surface expression of sialyl-X. These results
suggest that the reduced expression of X in myeloblasts is related to the
presence of the strong 6'-sialyltransferase, which uses the precursor
substrate at the expense of the 3-fucosyltransferase and prevents the
synthesis of X and sialyl-X. The developmental regulation of the levels of
3'- and 6'-sialyltransferases, and the level and specificity of the
3-fucosyltransferases, therefore controls the expression of X and its
degree of sialylation.
Volume 78,
Issue 6,
pp. 1452-1460,
09/15/1991
Copyright © 1991 by The American Society of Hematology

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