TOPOISOMERASE-II EXPRESSION IN NORMAL HEMATOPOIETIC-CELLS AND CHRONICLYMPHOCYTIC-LEUKEMIA - DRUG-SENSITIVITY OR RESISTANCE

Chronic lymphocytic leukaemia (CLL) is a progressive disease, commonly treated in its early stage with alkylating agents. A multi-agent regi men which includes anthracyclines is used to treat advanced disease. D espite chemotherapy, the disease remains incurable. There is now consi derable 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 investig ated topoisomerase II mRNA expression in 34 CLL patients and in haemop oietic cells from 10 normal donors. Expression was found to be low but detectable in all patients and normals. Such low levels may contribut e to the toxicity of alkylating agents, but could severely limit the e ffect of anthracyclines.