The inhibitory effects of a 1 h exposure to pharmacologically relevant concentrations of the anthracenedione mitoxantrone were assessed with respect to the in vitro clonogenic growth of leukemic myeloblasts obtained from patients with acute myelogenous leukemia (AML). A steep mitoxantrone dose-response curve was observed, and increases in drug concentrations at both low and high dose ranges were associated with a significant potentiation of anti-leukemic effects. In particular, mitoxantrone concentrations of 1 microM or greater were highly inhibitory to leukemic blast progenitor cell growth, and were also effective in reducing or eliminating leukemic cell self-renewal capacity in those samples assayed. These findings suggest that mitoxantrone mediated lethal effects towards leukemic cells are dose-related within a pharmacologically achievable range, and raise the possibility that an increase in plasma levels through dose escalation might lead to enhanced leukemic cell killing in vivo.