Inhibition of FLT3 by the PTK inhibitor SU5614 induces apoptosis in AML-derived cell lines expressing a constitutive active FLT3.

(A) MM6 cells were treated with 5 μM SU5614 for 48 hours and were analyzed by flow cytometry after staining with annexin V–PE and 7-AAD. Representative dot plots from 1 of 3 independently performed experiments are shown. (B) MM6 cells were treated as described in panel A with SU5614 and the percentage of cell nuclei showing a hypodiploid DNA content was analyzed after staining with PI by flow cytometry. A representative histogram of 3 independent experiments is shown. (C) Dose-response curve of the apoptosis-inducing activity of SU5614 in AML cell lines after 72 hours of incubation. Black bars represent early apoptotic cells (annexin V⁺/7-AAD⁻) and gray bars represent early and late apoptotic cells (annexin V⁺/7-AAD⁻ and annexin V⁺/7-AAD⁺). Cells were treated as described in panel A. Values represent means and SDs from 3 independent experiments.