Sensitivities of AML blast stem cells to idarubicin and daunorubicin: a comparison with normal hematopoietic progenitors.
The objective of this study was to determine whether or not cell culture studies could contribute to the correct choice between idarubicin (IDA) and daunorubicin (DNR) for combination with ara-C in remission induction therapy of AML. Two growth factor-sensitive AML cell lines and the peripheral blood blast cells from 10 patients with AML were studied in culture for sensitivity to IDA and DNR under four culture conditions; cells were grown either in methylcellulose or suspension culture in the presence of G-CSF or GM-CSF. Normal bone marrow cells were cultured in methylcellulose in the presence of IDA or DNR under conditions suitable for the detection of BFU-E and CFU-C. Dose-response curves for AML blast cells were characterized by an initial shoulder and then an exponential decrease in survival. Marked patient-to-patient variation was observed for both portions of the survival curves. IDA was significantly more toxic to blast cells than DNR, especially for more sensitive cell populations. Consistent differences in drug sensitivity in the four culture conditions were not observed. BFU-E and CFU-C dose-response curves of normal marrow progenitors resembled those of AML blast cells but in contrast fell within a narrow range. The culture studies support the clinical finding in AML of modest superiority of IDA over DNR. The heterogeneity in sensitivity of AML blasts in culture suggests an opportunity to individualize treatment. Preclinical studies may help in developing such a therapeutic approach.
Curtis
J E
JE
Department of Medicine, Ontario Cancer Institute, Toronto, Canada.
Minden
M D
MD
Minkin
S
S
McCulloch
E A
EA
D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000473:pathology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D003630:Daunorubicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015255:Idarubicin; D003630:Daunorubicin