Effect of treating cells with the combination of adaphostin and STI571.

(A) K562 cells were incubated for 24 hours with the indicated concentration of adaphostin in the presence of diluent (open circles) or 20 μM STI571 (closed circles). At the completion of the incubation, cells were washed, plated in 0.3% agar, and incubated for 10 to 14 days before colony formation was assessed. Error bars, mean ± 1 SD for quadruplicate plates treated with the indicated drug concentration. (Inset) Cells were incubated for 24 hours with the indicated concentration of STI571 in the absence (open circles) or presence (closed circles) of 5 μM adaphostin. At the completion of the incubation, colony-forming ability was assessed as described for panel A. (B) K562 cells were incubated for 24 hours with the indicated concentration of adaphostin in the presence of diluent (open circles) or 10 μM STI571 (closed circles), fixed, and examined for apoptotic morphologic changes. Results in panels A and B are representative of 3 independent experiments. (C) Circulating mononuclear cells from a patient with CML were treated for 24 hours with the indicated concentrations of adaphostin in the absence (open circles) or presence (closed circles) of 20 μM STI571, washed, and plated in 0.3% agar containing 50 ng/mL G-CSF. After 8 days, granulocyte colonies were counted. (D) Summary of results obtained when the experiment depicted in panel C was performed on 6 CML samples.