Inhibition of primitive and committed progenitor growth following exposure to imatinib mesylate.

CD34⁺ cells from patients with CML or healthy donors were exposed to imatinib mesylate at the concentrations indicated for 96 hours. Subsequently, cells were assayed for primitive (A) and committed (B) progenitors. The mean ± SEM, graphed for CML (—▾—) and normal (- - ♦ - -) samples, is based on replicate experiments (CML, n = 5; normal, n = 4). Concentrations of imatinib mesylate at which CML progenitors were significantly suppressed compared with no exposure to imatinib mesylate are indicated by asterisks below the curve (3 asterisks, P < .001; 2 asterisks, P < .01; and 1 asterisk, P < .05). Concentrations of imatinib mesylate at which CML progenitor frequency was significantly different from normal progenitor frequency are indicated by daggers above the curve (3 daggers, P < .001; 2 daggers,P < .01; and 1 dagger, P < .05). (A) LTCIC frequency was calculated in limiting-dilution assays. The progenitor frequency normalized to the frequency of progenitors in the absence of imatinib mesylate is shown for each concentration of the drug. LTCIC frequency (mean ± SEM) in the absence of imatinib mesylate was 15 ± 10/1000 input CD34⁺ cells for CML samples and 7 ± 3/1000 cells for normal samples. (B) CFC frequency is plotted for each concentration of imatinib mesylate, normalized to the colony number obtained in the absence of imatinib mesylate. CFC frequency (mean ± SEM) in the absence of imatinib mesylate was 366 ± 87/1000 input CD34⁺ cells for CML samples and 101 ± 29/1000 cells for normal samples.