CEP-701 inhibits FLT3 autophosphorylation, inhibits proliferation, and induces apoptosis in FLT3-expressing human myeloid leukemia–derived cell lines.

Cells were incubated with CEP-701 for 1 hour to assay for phosphorylation, or 48 hours to assay for proliferation and annexin V binding.23 Immunoprecipitation and immunoblotting were performed as in Figure 1. The results for all 3 assays for each cell line are plotted on the same graph. MTT proliferation results (solid lines) are expressed as percent untreated (DMSO) control. Annexin V assay results (dashed lines) are expressed as percent cells lacking annexin V binding (ie, as percent of nonapoptotic cells). The immunoblots are shown on the insets (upper row, phosphorylated FLT3; lower row, total FLT3), and the densitometric analysis results of the immunoblots of phosphorylated FLT3 are graphed [solid lines, labeled P-FLT3]) as percent untreated (DMSO) control. (A) EOL-1. (B) MV4-11. (C) BV173. (D) HEL (immunoblot not shown because no FLT3 protein was detected).