The Gray Platelet Syndrome (GPS) is a rare inherited bleeding disorder characterized by deficiency of platelet α-granules, macrothrombocytopenia and marrow fibrosis. The autosomal recessive form of GPS is linked to loss of function mutations in NBEAL2, which is predicted to regulate granule trafficking in megakaryocytes, the platelet progenitors. We report the first analysis of cultured megakaryocytes from GPS patients with NBEAL2 mutations. Megakaryocytes cultured from peripheral blood or bone marrow hematopoietic progenitor cells from four patients were used to investigate megakaryopoiesis, megakaryocyte morphology and platelet formation. In vitro differentiation of megakaryocytes was normal, whereas we observed deficiency of megakaryocyte α-granule proteins and emperipolesis. Importantly, we first demonstrated that platelet formation by GPS megakaryocytes was severely affected, a defect which might be the major cause of thrombocytopenia in patients. These results demonstrate that cultured megakaryocytes from GPS patients provide a valuable model to understand the pathogenesis of GPS in humans.
Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients / C.A. Di Buduo, M.A. Alberelli, A.C. Glembostky, G. Podda, P.R. Lev, M. Cattaneo, R. Landolfi, P.G. Heller, A. Balduini, E. De Candia. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 6:1(2016 Mar 18), pp. 23213.1-23213.11.
|Titolo:||Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients|
|Parole Chiave:||aged; blood platelets; blood proteins; calcium; cell differentiation; cells, cultured; child; emperipolesis; gray platelet syndrome; humans; male; megakaryocytes; models, biological; mutation; young adult|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||18-mar-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/srep23213|
|Appare nelle tipologie:||01 - Articolo su periodico|