Background & Objective:  FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 ex...

BACKGROUND The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at earl...

Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) mutation have a poor prognosis, and FLT3 inhibitors are now under clinical investigation. PIM1, a serine/threonine kinase, is up-regulated in FLT3-ITD AML and may be involved in FLT3-mediated leukemogenesis. We employed a PIM1 inhibitor, AR00459339 (Array Biopharma Inc.), to investigate the effect of PIM1 in...

OBJECTIVES Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies in...

Mutation of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), which is one of the most frequent genetic alterations, strongly contributes to an increased risk of treatment failure and to poor prognosis. In this study, we established quantitative fragment analysis of FLT3-ITD simultaneously measuring mutant allele burden and length, verified the analytical performance and ev...

The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I-restricted immunogenic peptides. One of the tested p...

Pediatric acute myelogenous leukemia (AML) has a poor prognosis, and novel therapies are needed. The FLT3 tyrosine kinase represents a promising target in pediatric AML. FLT3 is constitutively activated either by an internal tandem duplication (ITD) or by a point mutation (PM) in 17% to 24% of pediatric AML cases. Autocrine stimulation of wild-type (WT) FLT3 by coexpressed FLT3 ligand (FL) occu...

OBJECTIVES Mutant forms FMS-like tyrosine kinase-3 (FLT3), are reported in 25% of childhood acute lymphoid leukemia (ALL) and 30% of acute myeloid leukemia (AML) patients. In this study, drug response, growth promoting, and protein trafficking of FLT3 wild-type was compared with two active mutants (Internal Tandem Duplication (ITD)) and D835Y. MATERIALS AND METHODS FLT3 was expressed on facto...

Acute myeloid leukemia (AML) with normal karyotype represents a clinically and molecularly heterogeneous disease. Molecular markers with prognostic significance have been examined to improve risk profile characterization of this group. Activating mutations on FLT3 receptor are one of the most common genetic alterations reported. However, the prevalence and prognostic significance of FLT3 geneti...

Activating mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor occur in approximately 30% of acute myeloid leukemia (AML) patients and, at least for internal tandem duplication (ITD) mutations, are associated with poor prognosis. FLT3 mutations trigger downstream signaling pathways including RAS-MAP/AKT kinases and signal transducer and activator of transcription-5 (STAT5). We find that...