Differentiation in Myelodysplastic, Myeloid Leukaemic and Normal Haemopoietic Cells: A New Approach Exploiting the Synergistic Interaction Between Differentiation Inducers and DNA Synthesis Inhibitors

  • G. E. Francis
  • J. E. T. E. Guimaraes
  • J. J. Berney
  • M. A. Wing
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 29)

Abstract

The normal haemopoietic system behaves as if proliferation and the differentiation transitions on and between the granulocytic, erythroid and other lineages are stochastic events governed by probabilities determined by the leveis of growth and differentiation Stimuli [1]. Recent studies of myeloid leukaemic and myelodysplastic(AML and MDS) cells suggest that, in contrast to cell lines, there is a shift in the balance of probabilities for proliferation and differentiation rather than a maturation block at any particular stage [2]. This in turn suggests that these cells retain many of the features of normal proliferation and differentiation and that they will be accessible to the same means of altering the proliferation- differentiation balance as in normal cells. We recently proposed that physiological and pharmacological agents which enhance differentiation and maturation in vitro act by two fundamentally different routes: (a) by hastening progression through various differentiation/maturation steps; and (b) by slowing proliferation by inhibition of DNA synthesis.

Keywords

Agar Cytosine Nism Diol Butyrate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Francis GE, Leaning MF (1984) Exp Haematol 13: 92–98Google Scholar
  2. 2.
    Guimaraes JE etal. (1985) Leuk Res (in press)Google Scholar
  3. 3.
    Bennet JM et al. (1982) Br J Haematol 51: 189–199Google Scholar
  4. 4.
    Francis GE, Hoffbrand AV In: Hoffbrand AV (ed) Recent advances in haematology. Churchill Livingstone, Edinburgh 1985 (in press)Google Scholar
  5. 5.
    Koeffler HP, Golde DW (1978) Blood 52: 355–361PubMedGoogle Scholar
  6. 6.
    Elstner E et al. (1983) In: Neth R, Gallo RC, Graves MF, Moore MAS, Winkler K (eds) Modern trends in human leukemia 5. New results in clinical and biological research including pediatric oncology. Springer, Berlin Heidelberg New York Tokyo (Haematology and blood transfusion vol 28 )Google Scholar
  7. 7.
    Francis GE et al. (1982) Exp Haematol 10 [Suppl 11]: 179–193Google Scholar
  8. 8.
    Editorial (1984) Lancet i: 943–944Google Scholar
  9. 9.
    Gold EJ et al. (1983) Cancer Treat Rep 67: 981–986PubMedGoogle Scholar
  10. 10.
    Besa EC et al. (1983) Blood 62 [Suppl 1]: 199aGoogle Scholar
  11. 11.
    Flynn PJ et al. (1983) Blood 62: 1211–1217PubMedGoogle Scholar
  12. 12.
    Moore MAS et al. (1983) In: Neth R, Gallo RC, Greaves MF, Moore MAS, Winkler (eds) Modern trends in human leukemia 5. New results in clinical and biological research including pediatric oncology. Springer, Berlin Heidelberg New York Tokyo (Haematology and blood transfusion vol 28 )Google Scholar
  13. 13.
    Novogrodsky A et al. (1983) Cancer 52: 9–14CrossRefGoogle Scholar
  14. 14.
    Boyd AV, Sullivan JF (1984) Blood 63: 384–392PubMedGoogle Scholar
  15. 15.
    Griffin J etal. (1982) Exp Hematol 10: 774–781PubMedGoogle Scholar
  16. 16.
    Tricot G et al. (1984) Br J Haematol 58: 231–240PubMedCrossRefGoogle Scholar
  17. 17.
    Solal-Celigny et al. (1984) Blood 63: 634–638PubMedGoogle Scholar
  18. 18.
    Housset M et al. (1982) Br J Haematol 51: 125–129PubMedCrossRefGoogle Scholar
  19. 19.
    Boyd AW, Metealf D (1984) Leuk Res 8: 27–43PubMedCrossRefGoogle Scholar
  20. 20.
    Tanaka M et al. (1975) Proc Natl Acad Sei USA 72: 1003–1006CrossRefGoogle Scholar
  21. 21.
    Yen A, Chiao JW (1983) Exp Cell Res 147: 87–93CrossRefGoogle Scholar
  22. 22.
    Mufti GJ et al. (1983) N Engl J Med 309: 1653–1654PubMedCrossRefGoogle Scholar
  23. 23.
    Pike BL, Robinson WA (1970) J Cell Physiol 76: 77–84PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • G. E. Francis
  • J. E. T. E. Guimaraes
  • J. J. Berney
  • M. A. Wing

There are no affiliations available

Personalised recommendations