Effect of pharmacologically relevant concentrations of mitoxantrone on the in vitro growth of leukemic blast progenitors.
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.
Grant
S
S
Division of Hematology/Oncology, Medical College of Virginia, Richmond 23298-0230.
Arlin
Z
Z
Gewirtz
D
D
Feldman
E
E
D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008942:Mitoxantrone / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D008942:Mitoxantrone