dc.creatorSalim, Juan Pablo
dc.creatorGlembotsky, Ana Claudia
dc.creatorLev, Paola Roxana
dc.creatorMarin Oyarzún, Cecilia Paola
dc.creatorGoette, Nora Paula
dc.creatorMolinas, Felisa Concepción
dc.creatorMarta, Rosana Fernanda
dc.creatorHeller, Paula Graciela
dc.date.accessioned2018-06-05T14:08:44Z
dc.date.accessioned2018-11-06T15:22:19Z
dc.date.available2018-06-05T14:08:44Z
dc.date.available2018-11-06T15:22:19Z
dc.date.created2018-06-05T14:08:44Z
dc.date.issued2016-12
dc.identifierSalim, Juan Pablo; Glembotsky, Ana Claudia; Lev, Paola Roxana; Marin Oyarzún, Cecilia Paola; Goette, Nora Paula; et al.; Differential expression of SDF-1 receptor CXCR4 in molecularly defined forms of inherited thrombocytopenias; Taylor & Francis Ltd; Platelets; 28; 6; 12-2016; 602-606
dc.identifier0953-7104
dc.identifierhttp://hdl.handle.net/11336/47286
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1896509
dc.description.abstractThe SDF-1-CXCR4 axis plays an essential role in the regulation of platelet production, by directing megakaryocyte (MK) migration toward the vascular niche, thus allowing terminal maturation and proplatelet formation, and also regulates platelet function in an autocrine manner. Inherited thrombocytopenias (IT) comprise a spectrum of diverse clinical conditions caused by mutations in genes involved in platelet production and function. We assessed CXCR4 expression and SDF-1 levels in a panel of well-characterized forms of IT. Decreased surface CXCR4 levels were found in 8 of 27 (29.6%) IT patients by flow cytometry, including 4 of 6 patients with ANKRD26-RT, 3 of 3 patients with GPS and 1 of 6 patients with FPD/AML. Low CXCR4 levels were associated with impaired SDF-1-triggered platelet aggregation, indicating that this decrease is functionally relevant, whereas a normal platelet response was shown in patients harbouring preserved membrane CXCR4. Reduced CXCR4 was not due to decreased gene expression, as platelet RNA levels were normal or increased, suggesting a post-transcriptional defect. Increased ligand-induced receptor internalization was ruled out, as circulating SDF-1 levels were similar to controls. MK CXCR4 expression was normal, indicating that the defect in CXCR4 arises after the step of platelet biogenesis. In conclusion, the finding of defective CXCR4 expression specifically associated with certain IT disorders highlights the fact that abnormalities in several megakaryocytic regulators underlie IT pathogenesis and further reveal the heterogeneous nature of these conditions.
dc.languageeng
dc.publisherTaylor & Francis Ltd
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1080/09537104.2016.1254763
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/09537104.2016.1254763
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectinherited thrombocytopenia
dc.subjectCXCR4
dc.subjectSDF-1
dc.titleDifferential expression of SDF-1 receptor CXCR4 in molecularly defined forms of inherited thrombocytopenias
dc.typeArtículos de revistas
dc.typeArtículos de revistas
dc.typeArtículos de revistas


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