Expression of topoisomerase II alpha in the G0/G1 cell cycle phase of fresh leukemic cells

Topoisomerase II alpha (topo II alpha) is the target enzyme for several ant ineoplastic drugs. Correlation between low expression of topo Ha and drug r esistance has been shown in vitro, but there is limited evidence of a corre lation to initial response to treatment or to overall prognosis. Normal cel ls express topo II alpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo II alpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of top o II alpha in leukemic cells from 25 patients with acute leukemia by flow c ytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed > 50% positive cells in G0/G1, and another five sa mples showed > 20%. This finding could possibly provide an explanation to p revious difficulties in correlating topo II alpha expression with clinical outcome. Six of eight patients, where > 20% of the cells in G0/G1 were posi tive for topo II alpha, entered CR, compared to one of five patients with < 20% topo II alpha positive cells in G0/G1. We suggest that topo II alpha e xpression in G0/G1 in leukemic cells may be of predictive value for clinica l response to cytostatic drugs. (C) 2001 Elsevier Science Ltd. All rights r eserved.