Increased activity of a specific sialyltransferase in chronic myelogenous leukemia.
Granulocytes from patients with chronic myelogenous leukemia (CML) are morphologically identical to their normal counterparts but show marked differences in circulation patterns and in some membrane properties. We have previously shown that there is abnormal lectin binding to CML granulocytes, and aberrant sialylation of membrane glycoproteins. To examine the changes in sialylation of CML granulocytes further, we have studied membrane preparations from CML and normal granulocytes for specific sialyltransferase activity. Because sialyltransferase enzymes are specific for the configuration of the acceptor group, enzyme activity was assayed by measuring transfer of sialic acid from CMP-14C-sialic acid to substrates of defined structure. As compared with those of normal counterparts, CML extracts catalyzed a 50% higher overall rate of sialylation of asialofetuin, a substrate possessing both N- and O-linked acceptors. Studies of enzyme specificity utilizing porcine and ovine submaxillary mucins, antifreeze glycoprotein and alpha-1 acid glycoprotein as acceptors showed that the increased sialylation by CML extracts was due primarily to substrates with the O-linked Gal beta 1----3GaINAc acceptor group. These data suggest that sialyltransferase activity is increased in CML granulocytes compared to normal granulocytes and that the increased enzyme activity is specific for O-linked Gal beta 1----3GaINAc. This enzyme activity may be directly responsible for the abnormal membrane sialylation and pathophysiological behavior of these cells.
Baker
M A
MA
Taub
R N
RN
Kanani
A
A
Brockhausen
I
I
Hindenburg
A
A
D001212:Asialoglycoproteins; D060748:Fetuins; D006098:Granulocytes / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000201:enzymology*; D009844:Oligosaccharides / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000378:metabolism
D001212:Asialoglycoproteins; D060748:Fetuins; D009844:Oligosaccharides; D000509:alpha-Fetoproteins; C017029:asialofetuin; D014166:Transferases; D012799:Sialyltransferases