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Detection of TNFα expression in the bone marrow and determination of TNFα production of peripheral blood mononuclear cells in myelodysplastic syndrome

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Pathology Oncology Research

Abstract

TNFα is a highly active cytokine which plays an important role in the regulation of apoptotic cell death, a mechanism involved in the pathophysiology of myelodysplastic syndrome (MDS). In this study we investigated the expression of TNFα of the bone marrow trephine biopsies by immunohistochemical method and the TNFα production of peripheral blood mononuclear cells by ELISA method in 15 patients affected by MDS. Five of seven patients without excess of blasts showed high or intermediate TNFα expression in the bone marrow biopsies, whereas two patients with excess of blasts were negative and one had low expression. The five CMML patients revealed low or intermediate expression. The production of TNFα by the PBMC was analysed in 10 patients, four patients with RA and two with CMML produced higher level of TNFα which increased after stimulation with phorbol myristic acetate, but none of the RAEB patients revealed increase in TNFα production. In conclusion we suppose that increased TNFα expression and production by PBMC may be an indirect evidence of the role of increased apoptosis in low risk MDS patients.

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References

  1. Alexandrakis M, Coulocheri S, Xylouri I, et al: Elevated serum TNF-α concentrations are predictive of shortened survival in patients with high-risk myelodysplastic syndromes. Haematologia 29:13–24, 1998.

    PubMed  CAS  Google Scholar 

  2. Bebôk Zs, Márkus B, Németh P: Prognostic relevances of transforming growth factor alpha (TGFα) and tumor necrosis factor alpha (TNFα) detected in breast cancer tissues by immunohistochemistry. Breast Cancer Res Treat 29:229–235, 1994.

    Article  PubMed  Google Scholar 

  3. Broxmeyer HE, Williams DE, Lu I, et al: The suppressive influence of human tumor necrosis factor on bone marrow hematopoietic progenitor cells from normal donors and patients with leukemia: synergysm of tumor necrosis factor and interferon-gamma. J Immunol 136, 4487–4495, 1986.

    PubMed  CAS  Google Scholar 

  4. Feneaux P: Molecular biology and apoptosis in myelodysplastic syndromes. ISH-EHA, Amsterdam, Education Session, 81–84, 1998.

    Google Scholar 

  5. Ganser A: Myelodysplastic syndromes (MDS): therapeutic drug interactions in the anti-death programme. Trends in OncoHemat. 6. 26–29, 1998.

    Google Scholar 

  6. Gersuk GM, Beckham C, Loken MR, et al: A role for tumour necrosis factor-α, Fas and Fas-ligand in marrow failure associated with myelodysplastic syndrome. Br J Haemat 103:176–188, 1998.

    Article  CAS  Google Scholar 

  7. Han J, Thompson P, Beutler B: Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J Exp Med 172:391–394, 1990.

    Article  PubMed  CAS  Google Scholar 

  8. Kitagawa M, Saito I, Kuwata T, et al: Overexpression of tumor necrosis factor (TNF)-α and interferon (IFN) -γ by bone marrow cells from patients with myelodysplastic syndromes. Leukemia 11:2049–2054, 1997.

    Article  PubMed  CAS  Google Scholar 

  9. Koike M, Ishiyama T, Tomoyasu S, et al: Spontaneous cytokine overproduction by peripheral blood mononuclear cells from patients with myelodysplastic syndromes and aplastic anemia. Leuk Res 19:639–644, 1995.

    Article  PubMed  CAS  Google Scholar 

  10. List AF, Brasfield F, Heaton R, et al: Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome. Blood 90:3364–3369, 1997.

    PubMed  CAS  Google Scholar 

  11. Maciejewski J, Selleri C, Anderson S, et al: Fas antigen expression on CD34+ human marrow cells is induced by interferon γ and tumor necrosis factor and potentiates cytokine-mediated hematopoietic suppression in vitro. Blood 85:3183–3190, 1995.

    PubMed  CAS  Google Scholar 

  12. Metcalf D: The molecular control of cell division, differentiation commitent and maturation in haemopoietic cells. Nature 339:27–30, 1989.

    Article  PubMed  CAS  Google Scholar 

  13. Musto P, Sanpaolo G, D’Arena G, et al. Serum levels of cytokines with hematopoietic activity in myelodysplastic syndromes (MDS). Brit J Haemat 102/1, suppl, 343 1998.

  14. Ogata K, Tamura H, Yokose N, et al: Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-γ and tumour necrosis factor-α in patients with myelodysplastic syndromes. Br J Haemat 90:15–21, 1995.

    Article  CAS  Google Scholar 

  15. Ohmori S, Ohmori M, Yamagishi M, et al: MDS-macrophage derived inhibitory activity on myelopoiesis of MDS abnormal clones. Br J Haemat 83:388–391, 1993.

    Article  CAS  Google Scholar 

  16. Parker JE, Foshlock KL, Mijovic A, et al: ‘Low risk’ myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of proversus anti-apoptotic bcl-2-related proteins. Br J Haematol 103:1075–1082, 1998.

    Article  PubMed  CAS  Google Scholar 

  17. Peddie CM, Wolf R, McLellan LI, et al: Oxidative DNA damage in CD34+ myelodysplastic cells is associated with intracellular redox changes and elevated plasma tumour necrosis factorconcentration. Br J Haemat 99:625–631, 1997.

    Article  CAS  Google Scholar 

  18. Rajapaksa R, Ginzton N, Rott LS, et al: Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells. Blood 88:4275–4287, 1996.

    PubMed  CAS  Google Scholar 

  19. Raza A, Gezer S, Mundle S, et al: Apoptosis in the bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes. Blood 86:268–276, 1995.

    PubMed  CAS  Google Scholar 

  20. Raza A, Gregory SA, Preisler HD: The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by dual actions of cytokines. Leuk Res 20:881–890, 1996.

    Article  PubMed  CAS  Google Scholar 

  21. Raza A, Mundle S, Iftikar A, et al: Simultaneous assessment of cell kinetics and programmed cell death in bone marrow biopsies of myelodysplastic syndrome reveals extensive apoptosis as the probable basis for ineffective hematopoiesis. Am J Hemat 48:143–154, 1995.

    Article  PubMed  CAS  Google Scholar 

  22. Sachs I: The control of hematopoiesis and leukemia: from basic biology to the clinic Proc Natl Acad Sci USA 93:4742–4749, 1996.

    Article  PubMed  CAS  Google Scholar 

  23. Seipelt G, Ganser A, Duranceyk H, et al: Induction of TNF-α in patients with myelodysplastic syndromes undergoing treatment with interleukin-3. Brit J Haemat 84:749–751, 1993.

    Article  PubMed  CAS  Google Scholar 

  24. Shetty V, Mundle S, Alvi S, et al: Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes. Leuk Res 20:891–900, 1996.

    Article  PubMed  CAS  Google Scholar 

  25. Stasi R, Brunetti M, Bussa S, et al: Serum levels of tumour necrosis factor-alpha predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome. Clin Lab Haematol 19:197–201, 1997.

    Article  PubMed  CAS  Google Scholar 

  26. Tsoplou P, Kouraklis-Symoenidis A, Thanopoulou E, et al: Apoptosis in patients with myelodysplastic syndromes: differential involvement of marrow cells in ‘good’ versus ‘poor’ prognosis patients and correlation with apoptosis-related genes. Leukemia 13:1554–1563, 1999.

    Article  PubMed  CAS  Google Scholar 

  27. Verhoef GEG, De Schouwer P, Ceuppens JL, et al: MA: Measurement of serum cytokine levels in patients with myelodysplastic syndromes. Leukemia 6:1268–1272, 1992.

    PubMed  CAS  Google Scholar 

  28. Visani G, Zauli G, Tosi P, et al: Impairment of GM-CSF production in myelodysplastic syndromes Br J Haemat 84:227–231, 1993.

    Article  CAS  Google Scholar 

  29. Yoshida Y, Mufti GJ: Apoptosis and its significance in MDS: controversies revisited. Leuk. Res 23:777–785, 1999.

    Article  PubMed  CAS  Google Scholar 

  30. Zoumbos N, Symeonidis A, Kourakli A, et al: Increased levels of soluble interleukin-2 receptors and tumor necrosis factor in serum of patients with myelodysplastic syndromes. Blood 77:413–414, 1991.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Ist Department of Internal Medicine, University Medical School of Pécs, Ifjúság str. 13, 7624, Pécs, Hungary

    Lenke Molnár, Alizadeh Hussain & Hajna Losonczy

  2. Department of Immunology and Biotechnology, University Medical School of Pécs, Hungary

    Tímea Berki & Péter Németh

Authors
  1. Lenke Molnár
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  2. Tímea Berki
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  3. Alizadeh Hussain
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  4. Péter Németh
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  5. Hajna Losonczy
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Molnár, L., Berki, T., Hussain, A. et al. Detection of TNFα expression in the bone marrow and determination of TNFα production of peripheral blood mononuclear cells in myelodysplastic syndrome. Pathol. Oncol. Res. 6, 18–23 (2000). https://doi.org/10.1007/BF03032653

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  • DOI: https://doi.org/10.1007/BF03032653

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