Background and Aims: Multiple myeloma is a malignant proliferation of plasma cells derived from a single clone. The tumor, its products and the host response lead to organ damages. Some factors that are responsible in its pathogenesis are recognized. As FMS like Tyrosine Kinase 3 receptor (FLT3) mutation has been proved as a determining factor in leukemic patients the goal of this study was to ...

Acute myeloid leukemia (AML), a hematologic malignancy that results in bone marrow failure, is the most common acute adults. The presence of FMS-related tyrosine kinase 3 (FLT3) mutations associated with poor prognosis, making evaluation FLT3-inhibitors an imperative goal clinical trials. Midostaurin was first FLT3-inhibitor approved by FDA and EMA for treatment FLT3-mutated AML, it showed sign...

Activating mutations of the FLT3 gene occur because of an internal tandem duplication of the juxta-membrane domain (FLT3/ITD) or point mutation of the activation loop domain (FLT3/ALM). The presence of FLT3 mutations as well as the allelic ratio of FLT3/ITD (ITD-AR, mutant– wild type ratio) may have prognostic significance. FLT3 mutation status of 630 children with de novo acute myeloid leukemi...

In acute myeloid leukemia (AML), two clusters of activating mutations are known in the FMS-like tyrosine kinase-3 (FLT3) gene: FLT3-internal tandem duplications (FLT3-ITDs) in the juxtamembrane (JM) domain in 20% to 25% of patients, and FLT3 point mutations in the tyrosine-kinase domain (FLT3-TKD) in 7% to 10% of patients, respectively. Here, we have characterized a new class of activating poin...

Although FLT3 mutations are essentially found in myeloid-lineage leukemia cells, a high level of FLT3 expression was recently observed in MLL gene-rearranged acute lymphoblastic leukemia without FLT3 mutations. Here, we analyzed the biologic and clinical significance of the FLT3 transcript level in comparison with several gene alterations in 181 de novo acute myeloid leukemia (AML) cases. The m...

background: the secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor (pml-rara) fusion gene may contribute to the acute promyelocytic leukemogenesis. chromosomal alterations and mutation of flt3 (fms-like tyrosine kinase 3) tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. however, the prognostic significance of flt3 mutat...

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...

Early signal relay steps upon ligand binding to the receptor tyrosine kinase Flt3 (ie, sites of Flt3 autophosphorylation and subsequent docking partners) are mainly unresolved. By immunoprecipitation of specific tryptic peptides contained in the juxtamembrane region of human Flt3 and subsequent radiosequencing, we identified the tyrosine residues 572, 589, 591, and 599 as in vivo autophosphoryl...

We characterized the mutational status of the FLT3 tyrosine kinase domain (FLT3-TLD) in 3082 patients with newly diagnosed AML. FLT3-TKD mutations were detected in 147 of 3082 (4.8%) patients. Similar to the FLT3 juxtamembrane domain mutations (FLT3-LM), there was a high correlation of FLT3-TKD mutations with normal karyotype (88 of 1472; 6.0%). FLT3-TKD mutations were most frequent in the AML ...