Preferential inhibition by cytarabine of CFU-GM from patients with chronic granulocytic leukemia

Abstract

Granulocyte-macrophage colony-forming (CFU-GM) cells from peripheral blood of normal subjects and patients with chronic granulocytic leukemia (CGL) were cultured in soft agar. Drugs under study were added in a liquid overlay 2 days after initiation of cultures, providing prolonged exposure to these agents thereafter. Dose-dependent inhibition of colony growth was recorded with each of eleven agents examined, and at the higher concentrations tested, colony formation was often completely suppressed. Cytarabine showed selectivity against CFU-GM from patients in the chronic stage of CGL (P = 0.006); the median 50% inhibitory concentration for 12 such patients was 3.4 ng/ml versus 11.8 ng/ml for 15 healthy subjects. Such selectivity was not found with busulfan, hydroxyurea, mercaptopurine, thioguanine, daunorubicin, vincristine, vinblastine, methotrexate, desacetylmethylcolchicine, and trimethylcolchicinic acid. One other group has also reported a preferential effect of cytarabine against colony-forming cells from patients with CGL, and this appears to be the only drug for which such selective activity has been recorded to date.