 the inhibition of differentiation and persistence of proliferation in cell transformation is probably not only caused by the mutation of single genes . 
 an additional mechanism of transcriptional control , not only of single genes but of gene programs , is possibly the alteration of the topoisomerases . 
 these enzymes regulate the conformation of dna by twisting and unwinding the double strands . 
 as has been shown previously , only the genes located in relaxed dna areas are transcribed and , therefore , the topoisomerases can be described as a gene regulation device . 
 we present the hypothesis that topoisomerase ii action is not only altered in , but also necessary for , hl-60 granulocytic cell differentiation . 
 thus , alteration of topoisomerases may well be a molecular mechanism of cellular differentiation.imagesfigure 1.figure 2 . 
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