Flt3-internal tandem duplications (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). We recently reported arsenic trioxide (ATO) and Flt3 inhibition synergize to induce apoptosis in Flt3-ITD cells. However, the signaling effect of ATO in these cells has not been elucidated. Here, we demonstrate that the treatment of ATO potently induces the activation of extracellular regulated...

The prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established and is of particular interest given the opportunities for targeted therapies using FLT3 inhibitors. We studied 203 patients with PML-RARA-positive APL; 43% of the patients had an FLT3 mutation (65 internal tandem duplications [ITDs], 19 D835/I836, 4 ITD+D835/I836). Both mutations were a...

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. Mutations in fms-like tyrosine kinase 3 (FLT3) gene including internal tandem duplication (ITD) and point mutation in the tyrosine kinase domain (TKD) as well as in nucleoplasmin (NPM1) gene are associated with pathogenesis of acute myeloblastic leukemia (AML)....

Gain-of-function mutations in the RAS and FLT3 genes are frequently found in cells of acute myeloid leukemia (AML), leading to constitutive activation of signaling pathways that regulate fundamental cellular processes, and are therefore attractive targets for AML therapy. The multi-targeted kinase inhibitor sorafenib is efficacious in AML with FLT3-internal tandem duplication (ITD), but resista...

BACKGROUND Fms-like tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutation is related to poor prognosis in normal-karyotype acute myeloid leukemia (AML). However, the prognostic significance of the mutation at relapse has not been adequately investigated. We investigated the prognostic significance of the FLT3 ITD mutation at relapse in normal-karyotype AML patients. METHODS We ana...

BACKGROUND Mutations in NPM1 and FLT3 genes represent the most frequent genetic alterations and important diagnostic and prognostic indicators in patients with acute myeloid leukemia (AML). OBJECTIVE We investigated the prevalence and clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo AML including adults and children. RESULTS NPM1 mutation was found in 21% and F...

INTRODUCTION In recent years, Fms-like tyrosine kinase (FLT) 3 has been the subject of several studies as a prognostic marker. OBJECTIVE In this study, the presence of FLT3 mutations in childhood acute leukemias patients and their association with prognosis were investigated. MATERIALS AND METHODS A total of 120 patients, 80 with acute lymphoblastic leukemia (ALL) and 40 with acute myelobla...

The mechanism of cell transformation by Fms-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia (AML) is incompletely understood. The most prevalent activated mutant FLT3 ITD exhibits an altered signaling quality, including strong activation of the STAT5 transcription factor. FLT3 ITD has also been found partially retained as a high-mannose precursor in an intracellular compartment. To anal...

Aberrant activations of Fms-like tyrosine receptor kinase (FLT) 3 are implicated in the pathogenesis of 20% to 30% of patients with acute myeloid leukemia (AML). G-749 is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G-749 retained its inhibitory potency ...