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Cytokine expression in B-CLL in relation to disease progression andin vitro activation

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Abstract

Earlier, we reported an association between lowin vitro andin vivo IL-1 and IL-6 production, decreased IL-1β and IL-10 mRNA expression and B cell chronic lymphocytic leukemia (B-CLL) disease progression. We have now further investigated cytokine mRNA transcription in B-CLL cells and cytokine serum levels in B-CLL patients. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification of tumor necrosis factor (TNFα), IFNγ, IL-6 and BCGF was equally often seen in non-progressive and progressive patients. However, 4 out of 23 non-progressive cases expressed mRNA for IL-12 while no IL-12 expression was seen in 15 progressive patients. No IL-12 was found in sera or supernatants fromin vitro stimulated B-CLL cells, whereas TNFα and IL-10 were detected in sera from 51 and 31 of 65 B-CLL patients, respectively. TNFα values were significantly high in sera from patients in stages III and IV with disease progression. TNFα and IL-10 were also detected in culture supernatants fromin vitro stimulated B-CLL cells, whereas IFNγ was undetectable in these cultures and rarely positive in serum. Although further investigations are required, our data and that from previous reports indicate that B-CLL-derived cytokines are involved in B-CLL disease progression.

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References

  1. Campana D, Coustan-Smith E, Kumagai MA, Manabe A. Growth requirements of normal and leukemic human B cell progenitors.Leuk Lymphoma 1994;13: 3595–371.

    Article  Google Scholar 

  2. Panayiotidis P, Jones D, Ganeshaguru K, Foroni L, Hoffbrand AV. Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cellsin vitro.Br J Haematol 1996;92: 97–103.

    Article  CAS  PubMed  Google Scholar 

  3. Mainou-Fowler T, Prentice AG. Modulation of apoptosis with cytokines in B-cell chronic lymphocytic leukemia.Leuk Lymphoma 1996;21: 369–377.

    Article  CAS  PubMed  Google Scholar 

  4. Juliusson G, Oscier DG, Fitchett Met al. Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosome abnormalities.N Engl J Med 1990;323: 720–724.

    Article  CAS  PubMed  Google Scholar 

  5. Aguilar-Santelises M, Mellstedt H, Jondal M. Leukemic cells from progressive B-CLL respond strongly to growth stimulationin vitro.Leukemia 1994;8: 1146–1152.

    CAS  PubMed  Google Scholar 

  6. O’Brien S, del Giglio A, Keating M. Advances in the biology and treatment of B-cell chronic lymphocytic leukemia.Blood 1995;85: 307–318.

    Article  PubMed  Google Scholar 

  7. Fournier S, Jackson J, Kumar Aet al. Low molecular weight B-cell growth factor (BCGF-12KD) as an autocrine growth factor in B cell chronic lymphocytic leukemia.Eur J Immunol 1992;22: 1927–1930.

    Article  CAS  PubMed  Google Scholar 

  8. Nilsson K, Larsson LG, Söderberg Oet al. On the role of endogenously produced TNFα and IL-6 as regulators of growth and differentiation of B-type chronic lymphocytic leukemia cellsin vitro.Curr Top Microbiol Immunol 1992;182: 271–277.

    CAS  PubMed  Google Scholar 

  9. Huang R, Tsuda H, Takatsuki K. Interleukin-2 prevents programmed cell death in chronic lymphocytic leukemia cells.Int J Hematol 1993;58: 83–92.

    CAS  PubMed  Google Scholar 

  10. Jewell AP, Worman CP, Lydyard PMet al. Interferon-alpha up-regulates bcl-2 expression and protects B-CLL cells from apoptosisin vitro andin vivo.Br J Haematol 1994;88: 268–274.

    Article  CAS  PubMed  Google Scholar 

  11. Van Kooten C, Rensink I, Aarden L, Van Oers R. Effect of Il-4 and IL-6 on the proliferation and differentiation of B-chronic lymphocytic leukemia cells.Leukemia 1993;7: 618–624.

    PubMed  Google Scholar 

  12. Takeuchi H, Katayama I. Interleukin 1 (IL-1α and IL-1β) induces differentiation/activation of B-cell chronic lymphoid leukemia cells.Cytokine 1994;6: 243–246.

    Article  CAS  PubMed  Google Scholar 

  13. Reittie JE, Yong KL, Panayiotidis P, Hoffbrand AV. Interleukin-6 inhibits apoptosis and tumour necrosis factor induced proliferation of B-chronic lymphocytic leukemia.Leuk Lymphoma 1996;22: 83–90.

    Article  CAS  PubMed  Google Scholar 

  14. Fluckiger AC, Durand I, Banchereau J. Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells.J Exp Med 1994;179: 91–99.

    Article  CAS  PubMed  Google Scholar 

  15. Egle A, Marschitz I, Posch B, Herold M, Greil R. IL-10 serum levels in B-cell chronic lymphocytic leukemia.Br J Hematol 1996;94: 211–212.

    CAS  Google Scholar 

  16. Pistoia V. Production of cytokines by human B-cells in health and disease.Immunol Today 1997;18: 343–350.

    Article  CAS  PubMed  Google Scholar 

  17. Buschle M, Campana D, Carding SRet al. Interferon γ inhibits apoptotic cell death in a B-cell chronic lymphocytic leukemia.J Exp Med 1993;177: 213–218.

    Article  CAS  PubMed  Google Scholar 

  18. Tangye SG, Raison RL. Human cytokines suppress apoptosis of leukaemic CD5+B-cells and preserve expression of bcl-2.Immunol Cell Biol 1997;75: 127–135.

    Article  CAS  PubMed  Google Scholar 

  19. Meyaard L, Hovenkamp E, Otto SA, Miedema F. IL-12 induced IL-10 production by human T cells as a negative feedback for IL-12-induced immune responses.J Immunol 1996;156: 2776–2782.

    Article  CAS  PubMed  Google Scholar 

  20. Rai KR, Sawitsky A, Cronkite EPet al. Clinical staging of chronic lymphocytic leukemia.Blood 1975;46: 219–234.

    Article  CAS  PubMed  Google Scholar 

  21. Silver RT, Sawitsky A, Rai KR, Holland JF, Glidewell O. Guidelines for protocol studies in chronic lymphocytic leukemia.Am J Hematol 1978;4: 343–358.

    Article  CAS  PubMed  Google Scholar 

  22. Sjöberg J, Aguilar-Santelises M, Sjögren AMet al. Interleukin-10 mRNA expression in B-cell chronic lymphocytic leukaemia inversely correlates with progression of disease.Br J Haematol 1996;92: 393–400.

    Article  PubMed  Google Scholar 

  23. Adami F, Guarini A, Pini Met al. Serum levels of tumor necrosis factor-alpha in patients with B-cell chronic lymphocytic leukaemia.Eur J Cancer 1994;30: 1259–1263.

    Article  Google Scholar 

  24. Aguilar-Santelises M, Amador JF, Mellstedt H, Jondal M. Low IL-1 beta production in leukemic cells from progressive B cell chronic leukemia (B-CLL).Leukemia Res 1989;13: 937–942.

    Article  CAS  Google Scholar 

  25. Aguilar-Santelises M, Magnusson R, Svenson SBet al. Expression of interleukin-1α, interleukin-1β and interleukin-6 in chronic B lymphocytic leukemia (B-CLL) cells from patients at different stages of disease progression.Clin Exp Immunol 1991;84: 422–428.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Aguilar-Santelises M, Loftenius A, Ljungh Cet al. Serum levels of helper factors (IL-1α, Il-1β and IL-6), T cell products (sCD4 and sCD8), sIL-2R and ß2 in patients with B-CLL and benign B lymphocytosis.Leukemia Res 1992;16: 607–613.

    Article  CAS  Google Scholar 

  27. Osorio LM, Jondal M, Aguilar-Santelises M. Regulation of B-CLL apoptosis through membrane receptors and bcl-2 family proteins.Leuk Lymphoma 1998;30: 247–256.

    Article  CAS  PubMed  Google Scholar 

  28. Söderberg O. Growth and survival of B-chronic lymphocytic leukaemia cells.Med Oncol 1998;15: 73–78.

    Article  PubMed  Google Scholar 

  29. Montserrat E. Chronic lymphoproliferative disorders.Curr Opin Oncol 1997;9: 34–41.

    Article  CAS  PubMed  Google Scholar 

  30. Kipps TJ. Chronic Lymphocytic leukemia.Curr Opin Hematol 1998;5: 244–253.

    Article  CAS  PubMed  Google Scholar 

  31. Dancescu M, Rubio-Trujillo M, Biron Get al. Interleukin-4 protects chronic lymphocytic leukemic B-cells from death by apoptosis and upregulates Bcl-2 expression.J Exp Med 1992;176: 1319–1326.

    Article  CAS  PubMed  Google Scholar 

  32. Paul WE. Interleukin-4, a prototype immunoregulatory lymphokine.Blood 1991;77: 1859–1870.

    Article  CAS  PubMed  Google Scholar 

  33. Schuler M, Huber C, Peschel C. Cytokines in the pathophysiology and treatment of chronic B-cell malignancies.Ann Hematol 1995;71: 57–63.

    Article  CAS  PubMed  Google Scholar 

  34. Decker T, Flohr T, Trautmann Pet al. Role of accessory cells in cytokine production by T cells in chronic B-cell lymphocytic leukemia.Blood 1995;86: 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  35. Hall SS. IL-12 at the cross-road.Science 1995;268: 1432–1434.

    Article  CAS  PubMed  Google Scholar 

  36. Sarfati M, Fournier S, Christoffersen M, Biron G. Expression of CD23 antigen and its regulation by IL-4 in chronic lymphocytic leukemia.Leukemia Res 1990;14: 47–55.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, (L8.3) Center for Molecular Medicine, Karolinska Hospital, S-171 76, Stockholm, Sweden

    M Aguilar-Santelises & A De Santiago

  2. Department of Oncology, Karolinska Hospital, Stockholm, Sweden

    H Mellstedt

  3. Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden

    D Gigliotti, LM Osorio & M Jondal

Authors
  1. M Aguilar-Santelises
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  2. D Gigliotti
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  3. LM Osorio
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  4. A De Santiago
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  5. H Mellstedt
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  6. M Jondal
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Correspondence to M Aguilar-Santelises.

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Aguilar-Santelises, M., Gigliotti, D., Osorio, L. et al. Cytokine expression in B-CLL in relation to disease progression andin vitro activation. Med Oncol 16, 289–295 (1999). https://doi.org/10.1007/BF02785875

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  • DOI: https://doi.org/10.1007/BF02785875

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