Skip to main content

Advertisement

SpringerLink
Log in

Patterns of adenosine deaminase, ecto-5′-nucleotidase, poly(A)polymerase and surface light chain expression in chronic lymphocytic leukemias

  • Original Article
  • Published:
Blut Aims and scope Submit manuscript

Summary

The levels of activity of three enzymes have been measured in the circulating malignant lymphocytes of 47 patients with B chronic lymphocytic leukemia (CLL). These were the purine degrative enzymes, adenosine deaminase (ADA) and ecto-5′-nucleotidase (5′NT) and the enzyme responsible for the polyadenylation of mRNA, poly(A) polymerase. The patterns of activity of the above enzymes and the expression of surface immunoglobulin light chains were examined. A heterogeneity in the specific activity of the enzymes was observed which could not be attributed to variations of the percentage of B lymphocytes. A positive correlation was found between ADA and poly(A)polymerase activity (r=0.383, p<0.01). Furthermore, the expression of immunoglobulin light chain phenotype was inversely related to 5′NT specific activity; CLL cases in which less than 20% of the cells expressed λ chain phenotype, presented 5′NT specific activity of 16.7±3.3 (S.E.) nmol/h/106 cells, whereas in CLL cases with more than 20% of the cells expressing this phenotype the enzyme specific activity was 4.8±1.6 (S.E.) nmol/h/106 cells (p<0.02). These findings suggest that the simultaneous determination of enzymatic activities and immunological markers, might be useful in defining subsets in CLL and the subsequent clinical treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Berger SL, Cooper HL (1975) Very short-lived and stable mRNAs from resting human lymphocytes. Proc Natl Acad Sci USA 72: 3872–3877

    Google Scholar 

  2. Boyum A (1968) Separation of leukocytes from blood and bone marrow. Scand J Clin Lab Invest [Suppl 97] 21; 1–3

    Google Scholar 

  3. Chaney AL, Marbach EP (1962) Modified reagents for determination of urea and ammonia. Clin Chem 8: 130–132

    Google Scholar 

  4. Coleman MS (1983) Selective enzyme inhibitors as antileukemic agents. BioScience 83: 707–712

    Google Scholar 

  5. Courtis CN, Trangas TT, Tsiapalis CM (1987) Increase in the levels of activity of polyadenylic acid-metabolizing enzymes following phytohaemagglutinin stimulation of human lymphocytes. Mol Cell Biochem 75: 33–42

    Google Scholar 

  6. Courtis N, Trangas T, Pangalis GA, Tsiapalis CM (1989) Correlation of poly(A)-polymerase and adenosine deaminase activity levels with cytotoxic effects of coformycin and 2′deoxycoformycin in cultured lymphocytes from patients with B-chronic lymphocytic leukemia. Clin Chem Enzymol Commun (in press)

  7. Edwards NL, Gelfand EW, Burk L, Dosch HM (1979) Distribution of 5′-nucleotidase in human lymphoid tissues. Proc Natl Acad Sci USA 76: 3474–3476

    Google Scholar 

  8. Foon KA, Todd RF (1986) Immunologic classification of leukemia and lymphoma. Blood 68: 1–31

    Google Scholar 

  9. Galton DAG (1982) The chronic leukaemias: Recent Advances in Haematology. Hoffbrand AV (ed), p 249. Churchill Livingston, London

    Google Scholar 

  10. Gordon J, Mellstedt H, Aman P, Biberfeld P, Bjorkholm M, Klein G (1983) Phenotypes in chronic B lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies. Identification of stages of maturation arrest and their relation to clinical findings. Blood 62: 910–916

    Google Scholar 

  11. Gordon J, Mellstedt H, Aman P, Biberfeld P, Klein G (1984) Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester induction of IgM secretion and changes in the expression of B cell-associated surface antigen. J Immunol 132: 541–547

    Google Scholar 

  12. Greaves M, Janossy G (1978) Patterns of gene expression and the cellular origins of human leukemias. Biochim Biophys Acta 516: 193–230

    Google Scholar 

  13. Green H, Chan T (1973) Pyrimidine starvation induced by adenosine in fibroblasts and lymphoid cells: role of adenosine deaminase. Science 182: 837–841

    Google Scholar 

  14. Hall JG (1963) Adenosine deaminase activity in lymphoid cells during antibody production. Aust J Exp Biol Med Sci 1: 93–96

    Google Scholar 

  15. Hamblin T, Hough D (1977) Chronic lymphocytic leukemia correlation of immunofluorescent characteristics and clinical features. Br J Haematol 36: 359–365

    Google Scholar 

  16. Hannam-Harris AG, Gordon J, Smith JL (1980) Immunoglobin synthesis by neoplastic B lymphocytes. Free light chain synthesis as a marker of B cell differentiation. J Immunol 125: 2177–2181

    Google Scholar 

  17. Hibi T, Sen Gupta S, Mackay A, Gelfand EW, Chechik BE (1984) Ecto-5′-nucleotidase II. Effect of 12-o-tetradecanoyl-phorbol 13-acetate on the expression of enzyme in normal and neoplastic B cell lines. J Natl Cancer Inst 73: 1081–1085

    Google Scholar 

  18. Ho PA, Dorken B, Ma DDF, Perruto A, Hunstein W, Hoffbrand AV (1986) Purine degrative enzymes and immunological phenotypes in B lymphocytic leukemia: indication that leukemia immunocytoma is a separate entity. Br J Haematol 62: 545–555

    Google Scholar 

  19. Hoffbrand AV, Ma DDF, Webster ADB (1982) Enzyme patterns in normal lymphocyte subpopulations, lymphoid leukaemias and immunodeficiency syndrome. Clin Haematol 11: 719–741

    Google Scholar 

  20. Hovi T, Smith JF, Allison AC, Williams SC (1976) Role of adenosine deaminase in lymphocyte proliferation. Clin Exp Immunol 23: 395–403

    Google Scholar 

  21. Ihle JN (1978) Experimental models and conceptual approaches to studies of lymphomas and leukemias: Etiology, biology and control. Semin Hematol 15: 95–115

    Google Scholar 

  22. Johnston AP (1982) Chronic lymphocytic leukemia and its relationship to normal B lymphopoiesis. Immunol Today 3: 343–348

    Google Scholar 

  23. Joly P, Devllier P, Pradier O (1986) A simple indirect immunofluorescence micromethod for cell typing. J Immunol Methods 93: 217–223

    Google Scholar 

  24. La Mantia M, Conklyn M, Quagliata F, Silber B (1977) Lymphocyte 5′-nucleotidase: Absence of detectable protein in chronic lymphocytic leukemia. Blood 50: 683–689

    Google Scholar 

  25. Ligler SF, Kettman JR, Smith RG, Frenkel EP (1983) Immunoglobulin phenotype on B cells correlates with clinical stage of chronic lymphocytic leukemia. Blood 62: 256–259

    Google Scholar 

  26. Lopes J, Zucker-Franklin D, Silber R. (1973) Heterogeneity of 5′-nucleotidase activity in lymphocytes in chronic lymphocytic leukemia. J Clin Invest 52: 1297–1300

    Google Scholar 

  27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1950) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  28. Ma DDF, Sylwestrowicz TA, Granger S, Massaia M, Franks R, Janossy G, Hoffbrand AV (1982) Distribution of terminal deoxynucleotidyltransferase and purine degrative and synthetic enzymes in subpopulations of human thymocytes. J Immunol 124: 1430–1435

    Google Scholar 

  29. Ma DDF, Sylwestrowicz T, Janossy G, Hoffbrand A (1983) The role of purine metabolic enzymes and terminal deoxynucleotidyltransferase in intrathymic T cell differentiation. Immunol Today 4: 65–68

    Google Scholar 

  30. Massaia M, Ma DDF, Sylwestrowicz TA, Tidman N, Price G, Janossy G, Hoffbrand AV (1982) Enzymes of purine metabolism in human peripheral lymphocyte subpopulations. Clin Exp Immunol 50: 148–154

    Google Scholar 

  31. Mellstedt H, Petterson D, Holm G (1978) Lymphocyte subpopulations in chronic lymphocytic leukemia (CLL). Relation to the activity of the disease. Acta Med Scand 204: 485–489

    Google Scholar 

  32. Pangalis GA, Tsavaris NB, Roussou PA (1984) The heterogeneity of 5′-nucleotidase activity in lymphoblasts of acute lymphoblastic leukemia, demonstrated by an improved cytochemical method. Biomed Pharmacother 38: 444–448

    Google Scholar 

  33. Pangalis GA, Trangas T, Papanastasiou CJ, Roussou PA, Tsiapalis CM (1985) Poly(A)polymerase activity in chronic lymphocytic leukemia of the B cell type. Acta Haematol 74: 31–34

    Google Scholar 

  34. Perez S, Courtis N, Kokkinopoulos D, Papamichail M, Tsiapalis CM, Trangas T (1987) A colorimetric assay for the determination of 5′-nucleotidase activity. J Immunol Methods 101: 73–78

    Google Scholar 

  35. Ramot B, Brok-Simoni F, Barnea N, Bank I, Holtzmann F (1977) Adenosine deaminase (ADA) activity in lymphocytes of normal individuals and patients with chronic lymphatic leukemia. Br J Haematol 36: 67–70

    Google Scholar 

  36. Rowe M, De Gast CG, Platts Mills TA, Asherson GL, Webster AD, Johnson SM (1979) 5′-nucleotidase of B and T lymphocytes isolated from human peripheral blood. Clin Exp Immunol 36: 97–101

    Google Scholar 

  37. Schröder HC, Schuster DK, Zahn RK, Müller WEG (1981) A novel metabolic effect of the adenosine deaminase inhibitor coformycin, a potentiator of antiviral adenosine analogues. Antiviral Res 1: 383–391

    Google Scholar 

  38. Sen Gupta S, Hibi T, Mackay A, Markovic V, Stein LD, Sigal N, Gelfand EW, Chechik BE (1984) Ecto-5′ nucleotidase I. Expression in human normal and neoplastic lymphoid cell lines representing sequential stages of B cell differentiation. J Natl Cancer Inst 73: 1075–1080

    Google Scholar 

  39. Simpkins H, Standon A, Davis BH (1981) Adenosine deaminase activity in lymphoid subpopulations and leukemias. Cancer Res 41: 3107–3110

    Google Scholar 

  40. Thompson LF, Ruedi JM, O'Connor RD, Bastian JF (1986) Ecto-5′-nucleotidase expression during human B-cell development. An explanation for the heterogeneity in B lymphocyte ecto-5′-nucleotidase activity in patients with hypogammaglobulinemia. J Immunol 137: 2496–2500

    Google Scholar 

  41. Trangas T, Courtis N, Pangalis GA, Cosmides HV, Ioannides C, Papmichail M, Tsiapalis CM (1984) Polyadenylic acid polymerase activity in normal and leukemic human leukocytes. Cancer Res 44: 3601–3617

    Google Scholar 

  42. Tsiapalis CM, Dorson JW, Bollum FJ (1975) Purification of terminal riboadenylate transferase from calf thymus gland. J Biol Chem 250: 4486–4496

    Google Scholar 

  43. Tung R, Silber R, Quagliata F, Conklyn M, Gottesman J, Hirschhorn G (1976) Adenosine deaminase activity in chronic lymphocytic leukemia. J Clin Invest 57: 756–761

    Google Scholar 

  44. Vives Corrons JL, Rocman C, Pujades A, Colomer D, Perez Vila E, Anegon I, Gallart T, Vives Puiggros J, Vinolas N, Montserrat E (1987) Combined assay of adenosine deaminase (ADA), purine phosphorylase (PNP) and lactate dehydrogenase (LDH) in the early evaluation of B-chronic lymphocyte leukemia. Am J Hematol (in press)

  45. Webster APB, Rowe M, Johnson S (1979) In: Ciba Foundation Symposium Series, no 68, p 135. Elsevier, Amsterdam

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Hellenic Anticancer Institute, 171 Alexandras Ave., 115 22, Athens, Greece

    Theoni Trangas, Nelly Courtis, Antonia Gounaris & Chris M. Tsiapalis

  2. Department of Immunology of the “G. Papanikolaou” Research Center of Oncology, Hellenic Anticancer Institute, 171 Alexandras Ave., 115 22, Athens, Greece

    Sonia Perez & Dimitris Kokkinopoulos

  3. Hematology Unit, First Department of Internal Medicine, University of Athens, 115 22, Athens, Greece

    Gerassimos A. Pangalis

Authors
  1. Theoni Trangas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nelly Courtis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonia Gounaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sonia Perez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dimitris Kokkinopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerassimos A. Pangalis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chris M. Tsiapalis
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trangas, T., Courtis, N., Gounaris, A. et al. Patterns of adenosine deaminase, ecto-5′-nucleotidase, poly(A)polymerase and surface light chain expression in chronic lymphocytic leukemias. Blut 58, 187–193 (1989). https://doi.org/10.1007/BF00320771

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00320771

Key words

Search

Navigation