Susceptibility of acute myeloid leukemia (AML) cells from clinically resistant and sensitive patients to daunomycin (DNR): assessment in vitro after stimulation with colony stimulating factors (CSFs).
Chemosensitivity of purified AML blasts to daunomycin was examined under conditions of CSF stimulation and compared with clinical outcome of DNR combination chemotherapy. AML blasts from 16 patients were purified, incubated serum-free in the presence of optimal concentrations of a complete cocktail of IL-3, GM-CSF and G-CSF to provoke cell proliferation maximally, and DNR drug sensitivity in vitro was assessed by inhibition of DNA synthesis in response to titrated DNR concentrations. The sensitivity of proliferating AML cells to DNR did not correlate with the clinical response of the patients as identical dose-response curves were obtained for complete responders (n = 6), partial responders (n = 5) and resistant cases (n = 5). As a major part of the AML population was induced to enter DNA synthesis in vitro, these data suggest that the manoeuvre of cell cycle stimulation has abrogated cellular resistance to daunomycin and rendered in vivo, apparently refractory cells susceptible to the anthracycline.
Santini
V
V
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Nooter
K
K
Delwel
R
R
Löwenberg
B
B
D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003115:Colony-Stimulating Factors; D003630:Daunorubicin