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Phorbol ester-induced differentiation of chronic lymphocytic leukaemia cells

Nature volume 288, pages 176–178 (1980)Cite this article

Abstract

The croton oil-derived tumour-promoting agent 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) exerts pleiotropic effects on the differentiation and proliferation of both normal and malignant animal and human cells in vitro. TPA is mitogenic in nanomolar concentrations to chicken embryo fibroblasts1 and human T lymphocytes2 and inhibits the terminal differentiation of various committed embryonic cells3,4 and mouse Friend erythroleukaemia5 or myeloid leukaemia6 cells. TPA induces a terminal cell differentiation in some murine7 and human7–11 myeloid leukaemia and histiocytic lymphoma cells12. We report here the effect of TPA on chronic lymphocytic leukaemia (CLL) biopsy cells in vitro. In four out of five CLL patients studied, TPA induced the appearance of 90–100% lymphoblastoid and plasmacytoid cells after 4 days of culture. Under the influence of TPA, 86–97% of the cells expressed with time increasing amounts of intracytoplasmic immunoglobulin (C-Ig) of the same phenotype as that detected on the surface (S-Ig) of fresh, non-induced CLL cells. A parallel decrease in both monoclonal S-Ig density and DN A synthesis of the CLL cells was observed. Electron microscopic studies showed a maturation towards plasma cells. We therefore conclude that TPA is capable of inducing differentiation of CLL cells in vitro.

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References

  1. Driedger, P. E. & Blumberg, P. M. Cancer Res. 37, 3257–3265 (1977).

    CAS  PubMed  Google Scholar 

  2. Touraine, J.-L. et al. J. exp. Med. 143, 460–465 (1977).

    Article  Google Scholar 

  3. Cohen, R., Pacifici, M., Rubinstein, N., Biehl, J. & Holtzer, H. Nature 266, 538–540 (1977).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Diamond, L., O'Brien, T. G. & Rovera, G. Nature 269, 247–248 (1977).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Rovera, G., O'Brien, T. & Diamond, L. Proc. natn. Acad. Sci. U.S.A. 74, 2894–2898 (1977).

    Article  ADS  CAS  Google Scholar 

  6. Kasukabe, T., Honma, Y. & Hozumi, M. Gann 70, 119–123 (1979).

    CAS  PubMed  Google Scholar 

  7. Lotem, J. & Sachs, L. Proc. natn. Acad. Sci. U.S.A. 76, 5158–5162 (1979).

    Article  ADS  CAS  Google Scholar 

  8. Huberman, E. & Callahan, M. F. Proc. natn. Acad. Sci. U.S.A. 76, 1293–1297 (1979).

    Article  ADS  CAS  Google Scholar 

  9. Rovera, G., Santoli, D. & Damsky, C. Proc. natn. Acad. Sci. U.S.A. 76, 2779–2783 (1979).

    Article  ADS  CAS  Google Scholar 

  10. Rovera, G., O'Brien, T. & Diamond, L. Science 204, 868–870 (1979).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Vorbrodt, A., Meo, P. & Rovera, G. J. Cell Biol. 83, 300–307 (1979).

    Article  CAS  PubMed  Google Scholar 

  12. Nilsson, K., Andersson, L. C., Gahmberg, C. G. & Forsbeck, K. in New Trends in Human Immunology and Cancer Immunotherapy (eds Serrou, B. & Rosenfeld, C.) (Holt-Saunders & Doin, in the press).

  13. Galton, D. A. G. et al. Br. J. Haemat. 27, 7–23 (1974).

    Article  CAS  Google Scholar 

  14. Böyum, A. Scand. J. clin. Lab. Invest. 21, suppl. 97 (1968).

  15. Pellegrino, M. A., Ferrone, S., Dierich, M. P. & Reisfeld, R. A. Clin. Immun. Immunopath. 3, 324–333 (1975).

    Article  CAS  PubMed  Google Scholar 

  16. Smith, J. L., Cowling, D. C. & Barker, C. R. Lancet i, 229–233 (1972).

    Article  Google Scholar 

  17. Wybran, J., Chantler, S. & Fudenberg, H. Lancet i, 126–129 (1973).

    Article  Google Scholar 

  18. Han, T. & Dadey, B. Cancer 43, 109–118 (1979).

    Article  CAS  PubMed  Google Scholar 

  19. Fu, S. M., Chiorazzi, N. & Kunkel, H. G. Immun. Rev. 48, 23–44 (1979).

    Article  CAS  PubMed  Google Scholar 

  20. Robèrt, K.-H. Immun. Rev. 48, 123–143 (1979).

    Article  PubMed  Google Scholar 

  21. Tötterman, T. H. et al. Human Lymphocyte Differentiation (submitted).

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Authors and Affiliations

  1. The Wallenberg Laboratory and the Departments of Internal Medicine and Pathology, University of Uppsala, Uppsala, Sweden

    Thomas H. Tötterman, Kenneth Nilsson & Christer Sundström

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  1. Thomas H. Tötterman
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  2. Kenneth Nilsson
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  3. Christer Sundström
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Tötterman, T., Nilsson, K. & Sundström, C. Phorbol ester-induced differentiation of chronic lymphocytic leukaemia cells. Nature 288, 176–178 (1980). https://doi.org/10.1038/288176a0

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