Development of drug resistance in cultured clonogenic leukemic blast cells during the clinical course of myeloblastic leukemia.

We studied changes in the drug sensitivity of clonogenic leukemic blast cells from patients with acute myeloblastic leukemia during clinical courses. These cells were assayed using the colony formation technique in methylcellulose culture. Various doses of each of two chemotherapeutic agents, daunorubicin and aclarubicin, were added at the start of culture, and drug sensitivities were measured in terms of percentage inhibition of leukemic blast colony formation. Clonogenic leukemic blast cells became less sensitive to the drugs which were administered to the patients during the course of the disease, suggesting that development of drug resistance in vivo may reflect the presence of dominant resistant populations of clonogenic leukemic blast cells in vitro.