Variation in Sensitivity of DNA Synthesis to Ara‐C in Acute Myeloid Leukaemia

Summary The sensitivity of DNA synthesis to ara‐C was measured in vitro in intact myeloblasts from patients with acute myeloid leukaemia (AML). Ara‐C concentrations of 1 nm to 100 μm were used and ara‐CTP production measured at the same concentrations. Maximum inhibition of DNA synthesis was 95% in all patients. At ara‐C concentrations above 1 μm there was little variation in sensitivity of DNA synthesis but at concentrations below 300 μm there was wide variation in inhibition. Ara‐CTP concentrations associated with 50% inhibition of DNA synthesis ranged from 0·034 to 1·0 pmol/106 cells. Variation in sensitivity of DNA synthesis to ara‐C could not be explained by differences in ara‐CTP production alone. Concentrations of 100 nm to 1 μm ara‐C in vivo may be desirable to produce greater than 50% inhibition of DNA synthesis in all patients’myeloblasts.