Comparative studies on the in vitro killing of human normal and leukemic clonogenic cells (CFUc) by daunorubicin, daunorubicinol, and daunorubicin-DNA complex

The sensitivity of normal and acute nonlymphocytic leukemia-derived granulocytic stem cells (colony-forming units in culture, CFUc), exposed to daunorubicin, daunorubicinol, or daunorubicin-DNA complex in short-term suspension culture in vitro was studied. Normal CFUc were found to be considerably more sensitive to daunorubicin than to daunorubicinol. Killing of normal marrow CFUc by daunorubicin was an exponential function of the dose within the time and dose range tested. The C₅₀ varied between 100 and 230 ng/ml medium, LD₃₇ between 53 and 79 ng/ml medium. The response of CFUc to daunorubicin-DNA complex was exponential with somewhat larger individual variations (C₅₀=100-330 ng/ml, LD₃₇=46-878 ng/ml). The in vitro sensitivity of leukemia-patient derived CFUc to daunorubicin showed a greater variation (C₅₀=127-454 ng/ml, LD₃₇=74-640 ng/ml) than that of normal-control derived CFUc. In comparative studies with the leukemia-derived CFUc, daunorubicin-DNA complex was more or as effective as the free drug in killing CFUc derived from some patients, but in killing the CFUc derived from other patients was far less effective than the free drug. The results indicate greater individual variations in the response of leukemia-derived than normal CFUc both to daunorubicin and to daunorubicin-DNA complex in vitro. The therapeutic relevance of the results is discussed.