Skip to main content
Log in

Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Summary

Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased β2-microglobulin (β2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bateman A, Singh A, Kral T, Solomon S (1989) The immunehypothalamic pituitary-adrenal axis. Endocr Rev 10: 92–112

    Google Scholar 

  2. Berson SA, Yalow RS (1968) Radioimmunoassay of ACTH in plasma. J Clin Invest 47: 2725–2728

    Google Scholar 

  3. Besedovsky H, Sorkin E (1977) Network of immunoneuroendocrine interactions. Clin Exp Immunol 27: 1–3

    Google Scholar 

  4. Besedovsky H, Sorkin E, Keller M, Miller J (1975) Changes in blood hormone levels during the immune response. Proc Soc Exp Biol Med 150: 466–470

    Google Scholar 

  5. Blalock JE (1984) Relationship between neuroendocrine hormones and lymphokines. In: Pick E (ed) Lymphokines. Orlando, FI: Academic, pp 1–13

    Google Scholar 

  6. Blalock JE (1984) The immune system as a sensory organ. J Immunol 132: 1067–1070

    Google Scholar 

  7. Blalock JE, Smith EM (1980) Human leukocyte interferon: structural and biological relatedness to adrenocorticotropic hormone and endorphins. Proc Natl Acad Sci USA 77: 5972

    Google Scholar 

  8. Boldt DH, Macdermott RP, Jorolan EP (1975) Interaction of plant lectins with purified human lymphocyte populations: binding characteristics and kinetics of proliferation. J Immunol 114: 1532–1536

    Google Scholar 

  9. Bruserud O, Degre M, Thorsby E (1986) Interleukin 2 and interferon — production and expression of interleukin 2 receptor by human mononuclear cells stimulated with mumps virus or phytohemagglutinin. Acta Pathol Microbiol Scand 94: 51–55

    Google Scholar 

  10. Catovsky D, Lauria F, Matutes E, Foa R, Mantovani V, Tura S, Galton DAG (1981) Increase in T gamma lymphocytes in B-cell chronic lymphocytic leukemia. II. Correlation with clinical stage and findings in B-prolymphocytic leukemia. Br J Haematol 47: 539–544

    Google Scholar 

  11. Chronic Leukemia-Myeloma Task Force (1973) Proposed guidelines for protocol studies. III. Chronic lymphocytic leukemia. Cancer Chemother Rep 4: 159–165

    Google Scholar 

  12. Claman HM (1972) Corticosteroids and lymphoid cells. N Engl J Med 287: 388–397

    Google Scholar 

  13. Davey FR, Kurec AS, Tomar RH, Smith JR (1987) Serum immunoglobulins and lymphocyte subsets in chronic lymphocyte subsets in chronic lymphocytic leukemia. Am J Clin Pathol 87: 60–65

    Google Scholar 

  14. Elves MW, Roath S, Israelis MC (1963) The response of lymphocytes to antigen challenge in vitro. Lancet 1: 806–807

    Google Scholar 

  15. Faure GC, Bene MC, Bolle-Chanal MH (1987) Expression of CD 25 (Tac antigen) in lymphoid leukemias and non-Hodgkin lymphomas. Eur J Haematol 38: 26–28

    Google Scholar 

  16. Foa R, Giovarelli M, Jemma C, Fierro MT, Lusso P, Ferrando ML, Lauria L, Forni G (1985) Interleukin-2 (IL 2) and interferon gamma production by T lymphocytes from patients with B-chronic lymphocytic leukemia: evidence that normally released IL-2 is absorbed by the neoplastic B-cell population. Blood 66: 614

    Google Scholar 

  17. Gahrton G, Zech L, Robért KH, Bird AG (1979) Mitogenic stimulation of leukemic cells by Epstein-Barr virus. Engl J Med 301: 438–440

    Google Scholar 

  18. Greenspan FS, Rapoport B (1991) Thyriod gland. In. Greenspan F (ed) Basic and clinical endocrinology. London Academic Press, pp 119–123

    Google Scholar 

  19. Gross HA, Ruder HJ, Brown K, Lipsett MB (1972) A radioimmunoassay for plasma corticosterone steroids. 20: 681–695

    Google Scholar 

  20. Grossman CJ (1984) Regulation of the immune system by sex steroids. Endocr Rev 5: 435–454

    Google Scholar 

  21. Grossman CJ (1985) Interactions between the gonadal steroids and the immune system. Science 227: 257–261

    Google Scholar 

  22. Herrmann F, Locher A, Philippen H, Jauer B, Ruhl H (1982) Imbalance of T-cell subpopulations in patients with chronic lymphocytic leukemia of the B-cell type. Clin Exp Immunol 49: 157–162

    Google Scholar 

  23. Juliusson G, Gahrton G (1988) Clinical implication of CLL cell proliferation in vitro. Nouv Rev Fr Hematol 30: 399–401

    Google Scholar 

  24. Juliusson G, Robért KH, Nilsson B, Gahrton G (1985) Prognostic value of B cell mitogen-induced and spontaneous thymidine up-take in vitro in chronic B-lymphocytic leukaemia cells. Br J Haematol 60: 429–435

    Google Scholar 

  25. Kay NE, Kaplan ME (1986) Defective T-cell responsiveness in chronic lymphocytic leukemia: analysis of activation events. Blood 67: 578–581

    Google Scholar 

  26. Kay NE, Johnson JD, Stanek R, Douglas SD (1979) T-cell subpopulations in chronic lymphocytic leukemia: abnormalities in distribution and in in vitro receptor maturation. Blood 54: 1979–1981

    Google Scholar 

  27. Korsmeyer SJ, Greene WC, Cossman J, Hsu SM, Jensen JP, Neckers LM, Marshall SL, Bakhshi A, Depper JM, Leonard WJ, Jaffe ES, Waldman TA (1983) Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia. Proc Natl Acad Sci USA 80: 4522–4525

    Google Scholar 

  28. Lanz O, Grillot-Courvalin C, Schmitt C, Fermand JP, Broet JC (1985) Interleukin 2 induced proliferation of leukemic human B cells. J Exp Med 161: 1225–1230

    Google Scholar 

  29. Litman P, Swan F, Cabanillas F, Tucker SL, McLaughlin P, Hagemeister FB, Rodriguez MA, Velasquez WS (1991) Prognostic value of serum B2-microglobulin in low-grade lymphoma. Ann Intern Med 114: 855–860

    Google Scholar 

  30. Makinodan T (1979) Control of immunologic abnormalities associated with aging. Mech Ageing Dev 9: 7–9

    Google Scholar 

  31. Mancini G, Carbonara AO, Heremans JF (1965) Immunochemical quantitation of antigens by single radial diffusion. Immunochemistry 2: 235–254

    Google Scholar 

  32. Markey GM, Alexander HD, Agen AND, McConell RE, Morris TCM, Robertson JH, Crockard AD, Bridges JM (1986) Enumeration of absolute numbers of T-lymphocyte subsets in B-chronic lymphocytic leukemia using an immunoperoxidase technique: relation to clinical stage. Br J Hematol 62: 257–273

    Google Scholar 

  33. Mills KHG, Worman CP, Cawley JC (1982) T-cell subsets in B-chronic lymphocytic leukemia. J Haematol 50: 710–712

    Google Scholar 

  34. Mittelman A, Denny T, Gebhard C, Cirrincione C, Kurland E, Kozinek L (1986) Analysis of T-cell subsets in B-cell chronic lymphocytic leukemia: a correlation with the stage of disease. Am J Hematol 16: 67–73

    Google Scholar 

  35. Munck A, Guyre PM, Holbrook NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5: 25–44

    Google Scholar 

  36. Nagata Y, Burger MM (1974) Wheat germ agglutinin: molecular characteristics and specificity for sugar binding. J Biol Chem 249: 3116–3122

    Google Scholar 

  37. Nicholson GL (1976) Trans-membrane control of the receptors on normal and tumor cells. II. Surface changes associated with transformation and malignancy. Biochem Biophys 458: 1–72

    Google Scholar 

  38. Panayotides P, Porwit A, Lenkei R, Reizenstein P (1987) Interleukin-2 can induce proliferation of leukemic B-cells in prolymphocytic leukemia. Eur J Haematol 38: 274–276

    Google Scholar 

  39. Papaaioannou D, Geggie P, Klassen J (1979) Study of serum β-2 microglobulin levels in breast cancer patients. Clin Chim Acta 99: 37–41

    Google Scholar 

  40. Perry RT, Kay NE (1986) Abnormal T-cell function in early-stage chronic lymphocytic leukemia (CLL) patients. Am J Hematol 22: 55–61

    Google Scholar 

  41. Rai KR, Sawitsky A, Cronkite EP, Chanana A, Levy RN, Pasternack BS (1975) Clinical staging of chronic lymphocytic leukemia. Blood 46: 1219–1223

    Google Scholar 

  42. Rey A del, Besedovsky HO, Sorkin E (1984) Endogenous blood levels of corticosterone control the immunological cell mass and B cell activity in mice. J Immunol 133: 572–575

    Google Scholar 

  43. Riley V (1981) Psychoneuroendocrins influences on immunocompetence and neoplasia. Science 212: 1100–1109

    Google Scholar 

  44. Robért KH, Juliusson G, Biberfeld P (1983) Chronic lymphocytic leukemia cells activated in vitro reveal cellular changes that characterize B-prolymphocytic leukaemia and immunocytoma. Scand J Immunol 17: 397–401

    Google Scholar 

  45. Rosemberg E (1979) Immunoreactivity of standards and reference preparations used in the radioimmunoassay of follicle-stimulating and luteinizing hormones in serum. J Clin Endocrinol 48: 163–166

    Google Scholar 

  46. Smith EM, Blalock JE (1981) Human lymphocyte production of ACTH and endorphin-like substances — association with leukocyte interferon. Proc Natl Acad Sci USA 78: 7530–7533

    Google Scholar 

  47. Talal N, Dauphinee MJ, Ahmed A, Christados P (1983) Sex factors in immunity and autoimmunity. In: Yamamura Y (ed) Progress in immunology. New York, Academic Press, pp 1589–1600

    Google Scholar 

  48. Taylor DS, Kern JA, Nowell PC (1986) IL-2 alone is mitogenic only for Tac-positive lymphocytes in human peripheral blood. J Immunol 138: 1620–1624

    Google Scholar 

  49. Terstappen LWMM, de Grooth BG, van Berkel W, Napel CHH, Greve J (1988) Abnormal distribution of CD 8 subpopulations in B-chronic lymphocytic leukemia identified by flow cytometry. Leuk Res 12: 551–557

    Google Scholar 

  50. Terstappen LWMM, de Grooth BG, Segers-Nolten I, Greve J (1990) Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia. Blut 60: 81–87

    Google Scholar 

  51. Utsinger PD (1975) Impaired T-cell transformation in chronic lymphocytic leukemia (CLL): demonstration of a blastogenesis inhibitory factor. Blood 46: 883–890

    Google Scholar 

  52. Warren L, Buck CA, Tuczunski GP (1978) Glucopeptide changes and malignant transformation: a possible role for carbohydrate in malignant behavior. Biochim Biophys Acta 516: 97–127

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Everaus, H., Lehtmaa, J., Luik, E. et al. Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients. Ann Hematol 65, 219–223 (1992). https://doi.org/10.1007/BF01703948

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01703948

Key words

Navigation