An in vitro model for acute myelogenous leukemia chemotherapy

A human acute myelogenous leukemia cell line that forms colonies in soft-gel culture (KG-1) was used to test the effect of various schedules and combinations of chemotherapeutic agents. For comparison, the drug sensitivity of normal human marrow myeloid clonogenic cells was tested. Cytosine arabinoside inhibited both the KG-1 and normal human colony-forming cells (CFC) approximately 25% after a 2-hour exposure, 50% after a 5-hour exposure, and 90% after a 24-hour exposure. Daunorubicin had nearly an equal cytotoxic effect on KG-1 and normal marrow CFC after a 2- to 72-hour exposure to the drug. Daunorubicin at 0.15 micrograms/ml produced nearly complete inhibition of colony-forming cells. Amphotericin B also inhibited colony formation. Amphotericin B and daunorubicin, when combined in culture, produced a synergistic suppression of normal and leukemic CFC. The antileukemic agent 5-azacytidine at a concentration of 0.1 micrograms/ml produced approximately 60% inhibition of colony formation. Cytidine partially rescued CFC when the nucleoside was added in seven-fold excess to cultures containing 5-azacytidine. Leukemic and normal marrow clonogenic cells have nearly the same sensitivity to each chemotherapeutic agent and combination. Human acute myelogenous leukemia lines may provide useful models for the development of new chemotherapeutic schedules and combinations.