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Biosynthesis of O-Glycans in Leukocytes from Normal Donors and from Patients with Leukemia: Increase in O-Glycan Core 2 UDP-GlcNAc:Galß3GalNAc-R (GlcNAc to GalNAc) ß(1–6)-N-Acetylglucosaminyltransferase in Leukemic Cells¹

Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada [I. B., W. K., H. S.]; Department of Gynecologic Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263 [K. L. M.]; Department of Medicine, Toronto General Hospital and University of Toronto, Toronto, Ontario M5G 1L7, Canada [D. R. S., M. A. B.]; and Department of Pathology, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27514 [W. K.]

We have studied the biosynthesis of altered O-glycan structures on leukocytes from patients with chronic myelogenous leukemia and with acute myeloblastic leukemia (AML). It has been shown previously that the activity of CMP-NeuAc:Galß1-3GalNAc-R (sialic acid to galactose) (2–3)-sialyltransferase (EC 2.4.99.4) is increased in leukocytes from patients with chronic myelogenous leukemia (M. A. Baker, A. Kanani, I. Brockhausen, H. Schachter, A. Hindenburg, and R. N. Taub, Cancer Res., 47: 2763–2766, 1987) and with AML (A. Kanani, D. R. Sutherland, E. Fibach, K. L. Matta, A. Hindenburg, I. Brockhausen, W. Kuhns, R. N. Taub, D. van den Eijnden and M. A. Baker, Cancer Res., 50: 5003–5007, 1990). This increased activity may in part be responsible for the hypersialylation observed in leukemic leukocytes; however, hypersialylation may also be due to changes in underlying O-glycan structures. To test this hypothesis, we have assayed in normal human granulocytes and leukemic leukocytes several glycosyltransferases involved in the synthesis and elongation of the four common O-glycan cores. UDP-GlcNAc:Galß1-3GalNAc-R (GlcNAc to GalNAc) ß(1–6)-GlcNAc transferase (EC 2.4.1.102), which synthesizes O-glycan core 2 (GlcNAcß1-6[Galß1-3]GalNAc), is significantly elevated in chronic myelogenous leukemia (4-fold) and AML (18-fold) leukocytes relative to normal human granulocytes. Neither normal nor leukemic cells show detectable activities of GlcNAc transferases which synthesize O-glycan core 3 (GlcNAcß1-3GalNAc-R) and core 4 (GlcNAcß1-6[GlcNAcß1-3] GalNAc-R) or the blood group I structure. The ß3-GlcNAc transferase which elongates core 1 and core 2 was found at low levels in normal granulocytes but was not detectable in leukemic cells. The ß3-GlcNAc transferase and ß4-Gal transferase involved in poly-N-acetyllactosamine synthesis, as well as the ß3-Gal transferase synthesizing core 1 (Galß3 GalNAc), were present in all samples but were significantly increased in patients with AML. The observed changes are consistent with hypersialylation in leukemia.

¹ This research was supported by a grant from the Canadian Cystic Fibrosis Foundation (H. S.) and by grants from the National Cancer Institute of Canada and the Medical Research Council of Canada (M. A. B. and D. R. S.).

² To whom requests for reprints should be addressed, at Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

³ On leave from the University of North Carolina.

Received 9/ 4/90. Accepted 11/29/90.

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