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...

FLT3, a type III receptor tyrosine kinase, expresses on most acute leukemia cells as well as normal hematopoietic stem/progenitor cells. Mutation in the FLT3 gene is the most frequent genetic alteration in acute myeloid leukemia (AML) and is well known as an important driver mutation for the development of myeloid malignancies. FLT3 mutation is a strong poor prognostic factor for the long-term ...

The MLL-partial tandem duplication (PTD) associates with high-risk cytogenetically normal acute myeloid leukemia (AML). Concurrent presence of FLT3-internal tandem duplication (ITD) is observed in 25% of patients with MLL-PTD AML. However, mice expressing either Mll-PTD or Flt3-ITD do not develop AML, suggesting that 2 mutations are necessary for the AML phenotype. Thus, we generated a mouse ex...

BACKGROUND De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AML DNMT3A/FLT3/NPM1 ) has been suggested to represent a unique AML subset on the basis of integrative genomic analysis, but the clinical features of such patients have not been characterized systematically. METHODS We assessed the features of patients (n = 178) harboring mutations in DNMT3A, FLT3...

FLT3 receptor tyrosine kinase is expressed on lymphoid and myeloid progenitors in the hematopoietic system. Activating mutations in FLT3 have been identified in approximately 30% of patients with acute myelogenous leukemia, making it one of the most common mutations observed in this disease. Frequently, the mutation is an in-frame internal tandem duplication (ITD) in the juxtamembrane region th...

Salvage chemotherapy for relapsed/refractory FLT3-ITD-mutant acute myeloid leukemia (AML) is associated with a low complete remission (CR) rate (20–26%), despite the sequential use of a FLT3 inhibitor. FLT3 ligand rises precipitously after chemotherapy administration in advanced AML and is thought to have a detrimental effect on the activity of FLT3 inhibitors. Most studies involving FLT3 inhib...

Activating mutations in FLT3 (Fms-like tyrosine kinase 3) by internal tandem duplication (ITD) mutations are found in approximately 30% of patients with acute myeloid leukemia (AML) and are associated with poor outcome in this patient population. Numerous FLT3 inhibitors have been tested for the treatment of AML, but these inhibitors have shown variable responses that were attributed to heterog...

Activating mutations of the FLT3 receptor tyrosine kinase are common in acute myelogenous leukemia (AML) but are rare in adult acute lymphoblastic leukemia (ALL). We have recently shown that FLT3 is highly expressed and often mutated in ALLs with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome 11q23. Because hyperdiploid ALL samples also show high-level expression of FLT3, ...

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...

Mutations within the FMS-like tyrosine kinase 3 (FLT3) gene on chromosome 13q12 have been detected in up to 35% of acute myeloid leukemia (AML) patients and represent one of the most frequently identified genetic alterations in AML. Over the last years, FLT3 has emerged as a promising molecular target in therapy of AML. Here, we review results of clinical trials and of correlative laboratory st...