ArticleHaematologica2012
Two patterns of thrombopoietin signaling suggest no coupling between platelet production and thrombopoietin reactivity in thrombocytopenia-absent radii syndrome.
Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 31 citations in OpenAlex.
- The Y14-p53 regulatory circuit in megakaryocyte differentiation and thrombocytopenia.iScience · 2021Article
- Changes in megakaryopoiesis over ontogeny and their implications in health and disease.Platelets · 2020Review
- Inherited thrombocytopenia: novel insights into megakaryocyte maturation, proplatelet formation and platelet lifespan.Platelets · 2016Review
- Review
- Pathogenesis and management of inherited thrombocytopenias: rationale for the use of thrombopoietin-receptor agonists.International journal of hematology · 2013Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThrombocytopenia with absent radii syndrome is defined by bilateral radius aplasia and thrombocytopenia. Due to impaired thrombopoietin signaling there are only few bone marrow megakaryocytes and these are immature; the resulting platelet production defect improves somewhat over time. A microdeletion on chromosome 1q21 is present in all patients but is not sufficient to form thrombocytopenia with absent radii syndrome. We aimed to refine the signaling defect in this syndrome. DESIGN AND
methodsWe report an extended study of 23 pediatric and adult patients suffering from thrombocytopenia with absent radii syndrome in order to scrutinize thrombopoietin signal transduction by immunoblotting and gel electrophoretic shift assays. In addition, platelet immunotyping and reactivity were analyzed by flow cytometry. Results were correlated with clinical data including age and platelet counts.
resultsTwo distinct signaling patterns were identified. Juvenile patients showed abrogated thrombopoietin signaling (pattern #1), which is restored in adults (pattern #2). Phosphorylated Jak2 was indicative of activation of STAT1, 3 and 5, Tyk2, ERK, and Akt, showing its pivotal role in distinct thrombopoietin-dependent pathways. Jak2 cDNA was not mutated and the thrombopoietin receptor was present on platelets. All platelets of patients expressed normal levels of CD41/61, CD49b, and CD49f receptors, while CD42a/b and CD29 were slightly reduced and the fibronectin receptor CD49e markedly reduced. Lysosomal granule release in response to thrombin receptor activating peptide was diminished.
conclusionsWe show a combined defect of platelet production and function in thrombocytopenia with absent radii syndrome. The rise in platelets that most patients have during the first years of life preceded the restored thrombopoietin signaling detected at a much later age, implying that these events are uncoupled and that an unknown factor mediates the improvement of platelet production.
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