Fig. 3.
Effect of AG957 alone (▪) or AG957 plus CH11 (□) on CML (upper panels) and normal (lower panels) progenitors. The effects on CFU-Mix (A and D), BFU-E (B and E), and CFU-GM (C and F) are shown. To evaluate the combined effects of AG957 and CH11, untreated and AG957-treated (1 to 50 μmol/L for 30 minutes) CD34+cells (1 × 105/mL) were resuspended in serum-free medium and exposed (2 hours at 37°C) to CH11 (1 μg/mL). At the end of the incubation, CD34+ cells were incorporated in a standard methylcellulose assay to quantitate hematopoietic progenitors. Each histogram represents the mean (±SEM) percentage of inhibition from separate experiments using CML (n = 4) and normal (n = 2) CD34+ cells. For CML, control colonies per 1 × 103 CD34+ cells ranged from 2 to 7 for CFU-Mix, 39 to 80 for BFU-E, and 31 to 180 for CFU-GM. For normal samples, control colonies 1 × 103 CD34+cells ranged from 2 to 6 for CFU-Mix, 53 to 96 for BFU-E, and 97 to 154 for CFU-GM. When compared with cultures treated with AG957 alone (Wilcoxon signed-rank test), the inhibitory effect of AG957 plus Fas-L on CML progenitors was significantly different at the dose of 1 μmol/L for CFU-Mix (P = .04), BFU-E (P = .01), and CFU-GM (P = .04). For normal samples, no statistically significant difference was detected by comparing the inhibitory effects of AG957 or AG957 plus Fas-L. *Statistically significant when compared with samples treated with AG957 alone (Student’s t-test for unpaired data).