Glycosylation in Leukemia and Blood-Related Disorders

  • Inka Brockhausen
  • William Kuhns
Part of the Medical Intelligence Unit book series (MIU.LANDES)


Since cellular glycosylation appears to be a function of growth and differentiation, it is not surprising that in disease there are profound alterations of carbohydrate structures and the enzymes involved in their synthesis (Table 4). These complex alterations are difficult to classify, but based on many studies in this field we begin to understand emerging patterns.


Acute Myeloid Leukemia Sialic Acid HL60 Cell Chronic Myelogenous Leukemia Acute Myeloid Leukemia Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kuhns W, Primus F. Alteration of blood groups and blood group precursors in cancer. Prog Clin Biochem Med 1985; 2: 49–98.CrossRefGoogle Scholar
  2. 2.
    Shumak K, Beldotti L, Rachkewich R. Diagnosis of hematological disease using anti-i. Brit J Hematol 1979; 41: 399–405.CrossRefGoogle Scholar
  3. 3.
    Baker MA, Taub RN, Whelton CH et al. Aberrant sialylation of granulocyte membranes in chronic myelogenous leukemia. Blood 1984; 63: 1194–1197.PubMedGoogle Scholar
  4. 4.
    Baker MA, Taub RN, Kanani A et al. Increased activity of a specific sialyltransferase in chronic myelogenous leukemia. Blood 1985; 66: 1068–1071.PubMedGoogle Scholar
  5. 5.
    Taub R, Baker M, Madyastha K. Masking of neutrophil surface lectin binding sites in chronic myelogenous leukemia (CML). Blood 1980; 55: 294–303.PubMedGoogle Scholar
  6. 6.
    Baker MA, Kanani A, Hindenberg A et al. Changes in the granulocyte membrane following chemotherapy for chronic myelogenous leukemia. Br J Hematol; 1986; 62: 431–438.CrossRefGoogle Scholar
  7. 7.
    Fukuda M, Bothner B, Ramsamoo P et al. Structures of sialylated fucosyl polylactosaminoglycans isolated from chronic myelogenous leukemia cells. J Biol Chem 1985; 260: 12957–12967.PubMedGoogle Scholar
  8. 8.
    Fukuda M, Carlsson S, Klock J et al. Structures of 0-linked oligosaccharides isolated from normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells. J Biol Chem 1986; 261: 12796–12806.PubMedGoogle Scholar
  9. 9.
    Muroi K, Suda T, Nojiri H et al. Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl Le x and other lacto series type 2 chain antigens:absence of reactivity with normal hematopoietic progenitor cells. Blood 1992; 79: 713–719.PubMedGoogle Scholar
  10. 10.
    Carlsson S, Sasaki H, Fukuda M. Structural variations of 0-linked oligosaccharides present in leukosialin isolated from erythroid, myeloid, and T-lymphoid cell lines. J Biol Chem 1986; 261: 12787–12795.PubMedGoogle Scholar
  11. 11.
    Saitoh O, Piller F, Fox R et al. T-lymphocytic leukemia expresses complex, branched 0-linked oligosaccharides on a major sialoglycoprotein, leukosialin. Blood 1991; 77: 1491–1499.PubMedGoogle Scholar
  12. 12.
    Baker MA, Kanani A, Brockhausen I et al. Presence of cytidine 5’-monophospho-Nacetylneuraminic acid:Ga1131–3Ga1NAc-R a(2–3)-sialyltransferase in normal human leukocytes and increased activity of this enzyme in granulocytes from chronic myelogenous leukemia patients. Cancer Res 1987; 47: 2763–2766.PubMedGoogle Scholar
  13. 13.
    Kanani A, Sutherland DR, Fibach E et al. Human leukemic myeloblasts and myeloblastoid cells contain the enzyme cytidine 5’-monophosphate-N-acetylneuraminic acid:Ga1131–3Ga1NAc a(2–3)-sialyltransferase. Cancer Res 1990; 50: 5003–5007.PubMedGoogle Scholar
  14. 14.
    Brockhausen I, Kuhns W, Schachter H et al. Biosynthesis of 0-glycans in leukocytes from normal donors and from patients with leukemia:increase in 0-glycan core 2 UDPGIcNAc:Ga1131–3GalNAca-R (G1cNAc to GaINAc) ß(1–6)-N-acetylglucosaminyltransferase in leukemic cells. Cancer Res 1991; 51: 1257–1263.PubMedGoogle Scholar
  15. 15.
    Kuhns W, Rutz V, Paulsen H et al. Processing 0-glycan core 1, Ga1131–3GalNAca-R. Specificities of core 2, UDP-G1cNAc: Ga11313GalNAc-R(GlcNAc to GalNAc) 13–6-N acetylglucosaminyltransferase and CMP-sialic acid:Gal131–3GalNAc-R a3-sialyltransferase. Glycoconj J 1993; 10: 381–394.PubMedCrossRefGoogle Scholar
  16. 16.
    Ball ED, Vredenburgh JJ, Mills LE et al. Autologous bone marrow transplantation for acute myeloid leukemia following in vitro treatment with neuraminidase and monoclonal antibodies. Bone Marrow Transplant 1990; 6: 277–284.PubMedGoogle Scholar
  17. 17.
    Kuhns W, Oliver R, Watkins W et al. Leukemia-induced alterations of serum glycosyltransferase enzymes. Cancer Res 1980; 40: 268–275.PubMedGoogle Scholar
  18. 18.
    Skacel P, Watkins W. Significance of altered a-2-L-fucosyltransferase levels in serum of leukemic patients. Cancer Res 1988; 48: 3998–4001PubMedGoogle Scholar
  19. 19.
    Kuhns W, Pann C. Differentiation of HeLa cells with respect to blood group H antigen. Nature New Biology 1972; 96: 22–24.Google Scholar
  20. 20.
    Yoshimura M, Nishikawa A, Ihara Y et al. High expression of UDP-N-acetylglucosamine:13-D-mannoside 13–1,4-N-acetylglucosaminyltransferase III (GnT III) in chronic myelogenous leukemia in blastic crisis. Int J Cancer 1995; 60: 443–449.PubMedCrossRefGoogle Scholar
  21. 21.
    Yoshimura M, Ihara Y, Taniguchi N. Changes of 13–1,4-N-acetyl-glucosaminyltransferase III (GnT-III) in patients with leukaemia. Glycoconj J 1995; 12: 234–240.PubMedCrossRefGoogle Scholar
  22. 22.
    Brockhausen I, Reck F, Kuhns W et al. Substrate specificity and inhibition of UDPG1cNAc:G1cNAc131–2Manal-6R 131,6-Nacetylglucosaminyl-transferase V using synthetic substrate analogues. Glycoconj J 1995; 12: 371–379.PubMedCrossRefGoogle Scholar
  23. 23.
    de Korte D, Haverkort WA, de Boer M et al. Imbalance in the nucleotide pools of myeloid leukemia cells and HL-60 cells: correlation with cell-cyle phase, proliferation, differentiation, and transformation. Cancer Res 1987; 47: 1841–1847.PubMedGoogle Scholar
  24. 24.
    Augener W, Brittinger G, Schiphorst WECM et al. Activities and specificities of N-acetylneuraminyltransferases in leukemic cells. In:Neth R, Gallo RC, Greaves MF, Moore MAS, Winkler K eds. Hematology and Blood Transfusion. Vol. 28. Modern Trends in human leukemia V. Springer Verlag 1983: 135–138.Google Scholar
  25. 25.
    Rossowsky W, Srivastava B. Glycosyl transferase activities in leukemia cells from patients and human leukemic cell lines. Eur J Cancer Clin Oncol 1983; 19: 1431–1437.CrossRefGoogle Scholar
  26. 26.
    Suda K, Sakamoto S, Hida K et al. Electrofocusing pattern of fucosyltransferase activity in human leukemic cells. Cancer Res 1987; 47: 2782–2786.PubMedGoogle Scholar
  27. 27.
    Sarnesto A, Köhlin T, Hindsgaul O et al. Purification of the secretor-type 13-galactoside al-2 fucosyltransferase from human serum. J Biol Chem 1992; 267: 2737–2744.PubMedGoogle Scholar
  28. 28.
    Sarnesto A, Köhlin T, Hindsgaul O et al. Purification of the 13-N-acetylglucosiminide al-3 fucosyltransferase from human serum. J Biol Chem 1992; 267: 2745–2752.PubMedGoogle Scholar
  29. 29.
    Piller V, Piller F, Fukuda M. Biosynthesis of truncated 0-glycans in the T cell line Jurkat. J Biol Chem 1990; 265: 9264–9271.PubMedGoogle Scholar
  30. 30.
    Inoue M, Nakada H, Tanaka N et al. Tn antigen is expressed on leukosialin from T-lymphoid cells. Cancer Res 1994; 54: 85–88.PubMedGoogle Scholar
  31. 31.
    Thurnher M, Rusconi S, Berger EJ. Persistent repression of a functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome. J Clin Invest 1993; 91: 2103–2110.PubMedCrossRefGoogle Scholar
  32. 32.
    Lee N, Wang W, Fukuda M. Granulocytic differentiation of HL60 cells is associated with increase of poly-N-acetyllactosamine in Asn-linked oligosaccharides attached to human lysosomal membrane glycoproteins. J Biol Chem 1990; 265: 20476–20487.PubMedGoogle Scholar
  33. 33.
    Koenderman A, Wijermans P, van den Eijnden D. Changes in the expression of Nacetylglucosaminyltransferase III, IV, V associated with the differentiation of HL60 cells. FEBS Lett 1987; 222: 42–46.PubMedCrossRefGoogle Scholar
  34. 34.
    Nojiri H, Takaku F, Tetsuka T et al. Stimulation of sialidase activity during cell differentiation of human promyelocytic cell line HL60. Biochem Biophys Res Comm 1982; 104: 1239–1246.PubMedCrossRefGoogle Scholar
  35. 35.
    Robinson N, de Vries T, Davis R et al. Expression of fucosylated antigens and al -3 fucosyltransferases in human leukemia cell lines. Glycobiology 1994; 4: 317–326.PubMedCrossRefGoogle Scholar
  36. 36.
    Skacel P, Edwards A, Harrison C et al. Enzymic control of the expression of the X determinant (CD15) in human myeloid cells during maturation:the regulatory role of 61-sialyltransferase. Blood 1991; 78: 1452–1460.PubMedGoogle Scholar
  37. 37.
    Wilson A, Rider C. Evidence that leukosialin, CD43, is intensely sulfated in the murine T lymphoma line RDM-4. J Immunol 1992; 148: 1777–1783.PubMedGoogle Scholar
  38. 38.
    Juneja H, Schmalsteig F, Rajaraman S et al. Heterotypic adherence between murine leukemia/lymphoma cells and marrow stromal cells involves a recognition mechanism with galactosyl and mannosyl specificities. Exp Hematol 1992; 20: 405–411.PubMedGoogle Scholar
  39. 39.
    Metcalf D. The granulocyte-macrophage colony stimulating factors. Cell 1985; 43: 5–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Katlinsky A, Petrov R, Mikhailova A et al. Purification and properties of a 155 kDa bone marrow derived glycoprotein enhancing the activity of granulocyte-macrophage colony stimulating factor (GM-CSF). FEBS Lett 1993; 320: 67–70.PubMedCrossRefGoogle Scholar
  41. 41.
    Oh-eda M, Hasegawa M, Hattori K et al. 0-linked sugar chain of human granulocyte colony stimulating factor protects it against polymerization and denaturation allowing it to retain its biological activity. J Biol Chem 1990; 265: 11432–11435.Google Scholar
  42. 42.
    Cebon J, Nicola N, Ward M et al. Granulocyte-macrophage colony stimulating factor from human lymphocytes:effect of glycosylation on receptor binding and biological activity. J Biol Chem 1990; 265: 4483–4491.PubMedGoogle Scholar
  43. 43.
    Moonen P, Mermod J, Ernst J et al. Increased biological activity of deglycosylated recombinant human granulocyte/macrophage colony-stimulating factor produced by yeast or animal cells. Proc Natl Acad Sci USA 1987; 84: 4428–4431.PubMedCrossRefGoogle Scholar
  44. 44.
    Shibuya K, Chiba S, Miyagawa K et al. Structural and functional analyzes of glycosylation on the distinct molecules of human GM-CSF receptors. Eur J Biochem 1991; 198: 659–666.PubMedCrossRefGoogle Scholar
  45. 45.
    Hayashida K, Kitamura T, Gorman D et al. Molecular cloning of a second subunit of the receptor for the human GMCSF:Reconstitution of a high affinity GMCSF receptor. Proc Natl Acad Sci USA 1990; 87: 9655–9659.PubMedCrossRefGoogle Scholar
  46. 46.
    Gearing D, King J, Gough N et al. Expression cloning of a receptor for human granulocyte/macrophage colony stimulating factor. EMBO J 1989; 8: 3667–3676.PubMedGoogle Scholar
  47. 47.
    Ding DXH, Vera JC, ML Heaney et al. Nglycosylation of the human granulocyte-macrophage colony-stimulating factor receptor a subunit is essential for ligand binding and signal transduction. J Biol Chem 1995; 270: 24580–24584.PubMedCrossRefGoogle Scholar
  48. 48.
    Cyopick P, Culliton R, Brockhausen I et al. Role of aberrant sialylation of chronic myeloid leukemia granulocytes on binding and signal transduction by chemotactic peptides and colony stimulating factors. Leuk and Lymph 1993; 11: 79–90.CrossRefGoogle Scholar
  49. 49.
    Cheng J, Baumhueter S, Cacalano G et al. Hematopoietic defects in mice lacking the sialomucin CD34. Blood 1996; 87: 479–490.PubMedGoogle Scholar
  50. 50.
    Simmons D, Satterthwaite A, Tenen D et al. Molecular cloning of a cDNA encoding CD34, a sialomucin of hematopoietic stem cells. J Immunol 1992; 148: 267–271.PubMedGoogle Scholar
  51. 51.
    Berger EG, Kozdrowski I. Permanent mixed-field polyagglutinable erythrocytes lack galactosyltransferase activity. FEBS Lett 1978; 93: 105–108.PubMedCrossRefGoogle Scholar
  52. 52.
    Cartron J, Andrev J, Cartron J et al. Demonstration of T-transferase deficiency in Tnpolyagglutinate blood samples. Eur J Biochem 1978; 92: 111–119.PubMedCrossRefGoogle Scholar
  53. 53.
    Kobata A. Function and pathology of the sugar chains of human immunoglobulin G. Glycobiology 1990; 1: 5–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Narasimhan S, Lee J, Cheung R et al. 131,4-mannosyl glycoprotein 13–1,4-N-acetylglucosaminyl transferase III in human B and T lymphocyte lines and in tonsillar B and T lymphocytes. Biochem Cell Biol 1988; 66: 889–900.PubMedCrossRefGoogle Scholar
  55. 55.
    Frithz G, Ronquist G, Ericsson P. Serum sialyltransferase and fucosyltransferase activities in patients with multiple myeloma. Eur J Clin Oncol 1985; 21: 913–917.CrossRefGoogle Scholar
  56. 56.
    Okhura T, Isobe T, Yamashita K et al. Structures of the carbohydrate moieties of two monoclonal human k-type immunoglobulin light chains. Biochemistry 1985; 24: 503–508.CrossRefGoogle Scholar
  57. 57.
    Humphries DE, Sirokman G, Bing OHL. Enhanced galactosyltransferase expression in the failing hearts of spontaneously hypertensive rats. Biochem Biophys Res Comm 1996; 218: 320–324.PubMedCrossRefGoogle Scholar
  58. 58.
    Pirofsky B. In:Rose N, Mackay I eds. The Autoimmune Diseases. Academic Press, Orlando 1985: 469–491.Google Scholar
  59. 59.
    Crisp D, Pruzanski W. B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins). Am J Med 1982; 72: 915–922.PubMedCrossRefGoogle Scholar
  60. 60.
    Wu KK, Ku CSL, Chen Y-C. Reduced platelet sialyltransferase activity in patients with primary release disorder. Lancet 1980; 2: 440–443.CrossRefGoogle Scholar
  61. 61.
    Hardisty R. Disorders of platelets. II Functional abnormalities. In: Lilleyman J, Hann I. eds. Pediatric Hematology. Edinburgh: Churchill Livingstone, 1992: 167–199.Google Scholar
  62. 62.
    Peerschke EI, Zucker MB, Grant RA et al. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood 1980; 55: 841–847.PubMedGoogle Scholar
  63. 63.
    Gröttum KA, Solum NO. Congenital thrombocytopenia with giant platelets:a defect in the platelet membrane. Brit J Hemat 1969; 16: 277–289.CrossRefGoogle Scholar
  64. 64.
    Berndt MC, Gregory C, Chong BH et al. Additional glycoprotein defects in BernardSoulier’s syndrome:confirmation of genetic basis by parental analysis. Blood 1983; 62: 800–807.PubMedGoogle Scholar
  65. 65.
    Bithell T. Disorders of hemostasis and coagulation. In:Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN. eds. Wintrobe’s Clinical Hematology 9th ed. Vol 2. Philadelphia: Lea and Febiger, 1993: 1432–1433.Google Scholar
  66. 66.
    Lupu C, Rizescu M, Calb M. Altered distribution of some surface glycosaminoglycans and glycoconjugates on human platelets in diabetes mellitus. Platelets 1994; 5: 201–208.PubMedCrossRefGoogle Scholar
  67. 67.
    Sampietro T, Lenzi S, Cecchetti P et al. Nonenzymatic glycation of human platelet membrane proteins in vitro and in vivo. Clin Chem 1986; 32: 1328–1331.PubMedGoogle Scholar
  68. 68.
    Martinez J, Palascak JE, Kwasniak D. Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease. J Clin Invest 1978; 61: 535–538.PubMedCrossRefGoogle Scholar
  69. 69.
    Piller F, Le Deist F, Weinberg KI et al. Altered 0-glycan synthesis in lymphocytes from patients with Wiscott-Aldrich syndrome. J Exp Med 1991; 173: 1501–1510.PubMedCrossRefGoogle Scholar
  70. 70.
    Higgins E, Siminovitch K, Zhuang D et al. Aberrant 0-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the Wiskott-Aldrich syndrome. J Biol Chem 1991; 266: 6280–6290.PubMedGoogle Scholar
  71. 71.
    Piller F, Piller V, Fox R et al. Human T-lymphocyte activation is associated with changes in 0-glycan biosynthesis. J Biol Chem 1988; 263: 15146–15150.PubMedGoogle Scholar
  72. 72.
    Datti A, Orlaccio A, Siminovitch KA et al. Core 2 N-acetyl-glucosaminyltransferase activity:a diagnostic marker for WiskottAldrich syndrome. Glycosyl Dis 1994; 1: 127–135.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Inka Brockhausen
    • 1
  • William Kuhns
    • 1
  1. 1.Department of Biochemistry, Research Institute, Hospital for Sick ChildrenUniversity of TorontoTorontoCanada

Personalised recommendations