Topoisomerase II expression in normal haemopoietic cells and chronic lymphocytic leukaemia: drug sensitivity or resistance?

Chronic lymphocytic leukaemia (CLL) is a progressive disease, commonly treated in its early stage with alkylating agents. A multi-agent regimen which includes anthracyclines is used to treat advanced disease. Despite chemotherapy, the disease remains incurable. There is now considerable evidence to suggest that anthracyclines exert their effect via the nuclear enzyme topoisomerase II and that alterations in amount or activity of this enzyme may mediate drug resistance. We have investigated topoisomerase II mRNA expression in 34 CLL patients and in haemopoietic cells from 10 normal donors. Expression was found to be low but detectable in all patients and normals. Such low levels may contribute to the toxicity of alkylating agents, but could severely limit the effect of anthracyclines.