Alteration of topoisomerase II action is a possible molecular mechanism of HL-60 cell differentiation.

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.