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Diagram showing the difference between normal and mutated FLT3 genes with internal tandem duplications leading to ligand-independent activation and dimerization of receptor tyrosine kinase which causes uncontrolled cell proliferation and myeloid carcinoma.
Source publication
Detection of genetic mutations leading to hematological malignancies is a key factor in the early diagnosis of acute myeloid leukemia (AML). FLT3-ITD mutations are an alarming gene defect found commonly in AML patients associated with high cases of leukemia and low survival rates. Available diagnostic assessments for FLT3-ITD are incapable of combi...
Contexts in source publication
Context 1
... constitutes faithful, in-frame duplications of variable nucleotide lengths which deliver poor functionality to the JM domain, rendering the self-inhibitory system of the membrane protein disordered. The resulting changes negatively affect the activation of the protein, leading to auto-phosphorylation and, therefore, signal-independent cellular proliferation ( Figure 1) [4,5]. Additionally, the co-occurrence of FLT3-ITD with other mutations such as the mutations of nucleophosmin (NPM1) and DNA methyltransferase 3A (DNMT3A) are further reported [6,7], indicative of their importance as excellent genetic biomarkers for early and relapse diagnosis of AML in patients. ...
Context 2
... constitutes faithful, in-frame duplications of variable nucleotide lengths which deliver poor functionality to the JM domain, rendering the self-inhibitory system of the membrane protein disordered. The resulting changes negatively affect the activation of the protein, leading to auto-phosphorylation and, therefore, signal-independent cellular proliferation ( Figure 1) [4,5]. Additionally, the co-occurrence of FLT3-ITD with other mutations such as the mutations of nucleophosmin (NPM1) and DNA methyltransferase 3A (DNMT3A) are further reported [6,7], indicative of their importance as excellent genetic biomarkers for early and relapse diagnosis of AML in patients. ...
Citations
The creation of nanostructure is profound for the generation of nanobiosensors in several medical diagnosis. Here, we employed an aqueous hydrothermal route using Zinc-oxide (ZnO) and Gold (Au), which under optimal conditions formed an ultra-crystalline rose-like nanostructure textured with nanowires on the surface, coined as 'spiked nanorosette'. The spiked nanorosette structures was further characterized to possess crystallites of ZnO and Au grains with average sizes of 27.60 and 32.33 nm, respectively. The intensity for both ZnO (002) and Au (111) planes of the nanocomposite was inferred to be controlled by fine-tuning the percentage of Au nanoparticles doped in the ZnO/Au matrix, as referred by X-Ray diffraction analysis. The formation of ZnO/Au-hybrid nanorosettes were additionally verified by the distinct corresponding peaks from photoluminescence and X-ray photoelectron spectroscopy, supported by electrical validations. The biorecognition properties of the spiked nanorosettes were also examined using custom targeted and non-target DNA sequences. The DNA targeting capabilities of the nanostructures were analyzed by Fourier Transform Infrared and electrochemical impedance spectroscopy. The fabricated nanowire-embedded nanorosette exhibited a detection limit at the lower picomolar range of 1 × 10-12 M, with high selectivity, stability and reproducibility and good linearity, under optimal conditions. Impedance-based techniques are more sensitive to the detection of nucleic acid molecule whereas this novel spiked nanorosette demonstrate promising attributes as excellent nanostructures for nanobiosensor developments and their potential future application for nucleic-acids or disease diagnostics. This article is protected by copyright. All rights reserved.
