PURPOSE Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease. We show defects in the response of mutant FLT3 AML cells to the S-phase drug clofarabine that could account for the apparent contradiction. EXPERIMENTAL DESI...

FLT3 internal tandem duplication (ITD), one of the most frequent mutations in Acute Myeloid Leukemia (AML), is reported to be an unstable marker, as it can evolve from FLT3 ITD- to ITD+ during the disease course. A single-gene sensitive mutational screening approach may be helpful for better clarifying the exact timing of mutation occurrence, especially when FLT3 ITD appears to occur late, at d...

FMS-like receptor tyrosine kinase-3 (FLT3) belongs to the family of receptor tyrosine kinase (RTK), and the FLT3 mutation is observed in 1/3 of all acute myeloid leukemia (AML) patients. Potential FLT3 inhibitors have been investigated as potential therapeutic agents of AML. In this study, we identified a potent FLT3 inhibitor LDD1937 containing an indirubin skeleton. The potent inhibitory acti...

Purpose: Mutations in the receptor tyrosine kinase FLT3 are found in up to 30% of acute myelogenous leukemia patients and are associated with an inferior prognosis. In this study, we characterized critical tyrosine residues responsible for the transforming potential of active FLT3-receptor mutants and ligand-dependent activation of FLT3-WT. Experimental Design: We performed a detailed structure...

Acute myeloid leukemia is a malignant disease results from mutation in multipotent haemopoietic stemcell. The study aimed to investigate NPM1 and FLT3-ITD mutations Iraqi patients with AML correlateresults other clinical laboratory findings. Fifty-eight patients, admitted Baghdad TeachingHospital October 2019 till March 2020 addition 25 normal controls, were included the study.A detailed histor...

In the July 1, 2006, issue of Blood, Meshinchi et al1 comment on the role of stem-cell transplantation (SCT) in FLT3/ITD-positive acute myeloid leukemia (AML). In their interpretation of data previously presented by Gale et al,2 they conclude that the occurrence of a FLT3/ITD may not be regarded as a negative prognostic factor in patients undergoing allogeneic SCT. The dispute between both auth...

Background: Oncogenic mutation in the tyrosine kinase domain of FMS-Like 3 (FLT3-TKD) is a known recurrent AML.1 Com mon techniques used its detection and/or characterisation include Sanger sequencing and nextgeneration sequencing, with recognised sensitivity limitations.2 Aim/Objective: To validate use digital droplet PCR (ddPCR) quantification common FLT3-TKD mutations (D835Y, D835H, D835V). ...

Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in N...

PURPOSE CBL is a negative regulator of activated receptor tyrosine kinases (RTK). In this study, we determined the frequency of CBL mutations in acute leukemias and evaluated the oncogenic potential of mutant CBL. EXPERIMENTAL DESIGN The cDNA of 300 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL) patients and 82 human leukemic cell lines was ...