A novel FLT3 inhibitor FI-700 selectively suppresses the growth of leukemia cells with FLT3 mutations.

Purpose: The aim of this study was to evaluate the antileukemia activity of a novel FLT3 kinase inhibitor, FI-700.

Experimental Design: The antileukemia activity of FI-700 was evaluated in human leukemia cell lines, mutant or wild-type (Wt)-FLT3-expressing mouse myeloid precursor cell line, 32D and primary acute myeloid leukemia cells, and in xenograft or syngeneic mouse leukemia models.

Results: FI-700 showed a potent IC(50) value against FLT3 kinase at 20 nmol/L in an in vitro kinase assay.

Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia.

Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.