Differentiation in Myelodysplastic, Myeloid Leukaemic and Normal Haemopoietic Cells: A New Approach Exploiting the Synergistic Interaction Between Differentiation Inducers and DNA Synthesis Inhibitors
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 . 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 . 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.
KeywordsAgar Cytosine Nism Diol Butyrate
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