Patients with chronic myelogenous leukemia (CML) respond well to tyrosine kinase inhibitors (TKIs) of the Bcr-Abl oncoprotein. However, intolerance and resistance to these agents remains a challenge, and TKI’s are unable to eradicate rare leukemia-initiating cells. Leukemia treatment would benefit from a better understanding of molecular signals that are necessary for the survival of leukemia-initiating cells but dispensable for normal hematopoietic stem cells. Leukemia-initiating cells in CML can arise from myeloid progenitor cells, a population that we have reported in normal hematopoiesis to depend on the RNA-editing enzyme ADAR1 (adenosine deaminase acting on RNA-1). We now report that Bcr-Abl transformed leukemic cells were ADAR1-dependent in a conditional ADAR1 knockout mouse model. ADAR1 deletion reversed leukocytosis and splenomegaly, and preferentially depleted primitive Lin-Sca+Kit+ (LSK) leukemic cells but not LSK cells lacking the leukemic oncoprotein. ADAR1 deletion ultimately normalized the peripheral white blood count, eliminating leukemic cells as assessed by PCR. These results uncover a novel requirement for ADAR1 in myeloid leukemic cells and indicate that ADAR1 may comprise a new molecular target for CML-directed therapeutics.
A green synthesis carbon dots (CDs) with low cost and low toxicity was applied to establish fluorescent nanoprobe for measurement of glyphosate. The synthesis was realized by one-pot hydrothermal procedure...
A luminescent amino-functionalized metal–organic framework (Cu–MOFs) was synthesized from 2-aminoterephthalic acid and Cu(ii) ions by a solvothermal method.
In recent years, copper-based nanomaterials have been widely used in the study of glucose sensors because of its high sensitivity. In this work, a sensitive and selective electrochemical enzyme-free glucose sensor was successfully constructed using a composite of copper oxide nanowires (CuO NWs), molybdenum disulfide (MoS 2 ) and gold nanoparticle (AuNPs). This composite was systematically characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The sensor performance and interface property of the Au electrode modified by NF/AuNPs/CuO-MoS2 were measured by cyclic voltammetry (CV) and chronoamperometric measurements(i-t). Under optimal condition, the proposed sensor shows sensitivity value of 872.71 μA cm −2 mM −1 for glucose, with detection range from 0.5 μM to 5.67 mΜ and detection limit of 0.5 μM. The study also confirms satisfactory selectivity, reproducibility, and stability of the constructed sensor. This NF/AuNPs/CuO NWs-MoS 2 sensor performance toward normal human serum spiked with glucose is determined with RSD less than 4.71%, indicating superior potential for the practical quantitative analysis of glucose in serum samples.
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