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Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice.

Guerrero, Jose A; Bennett, Cavan; van der Weyden, Louise; McKinney, Harriet; Chin, Melody; Nurden, Paquita; McIntyre, Zoe; Cambridge, Emma L; Estabel, Jeanne; Wardle-Jones, Hannah; Speak, Anneliese O; Erber, Wendy N; Rendon, Augusto; Ouwehand, Willem H; Ghevaert, Cedric.
Blood; 124(24): 3624-35, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-25258341
NBEAL2 encodes a multidomain scaffolding protein with a putative role in granule ontogeny in human platelets. Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of α-granules within blood platelets and progressive bone marrow fibrosis. We present here a novel Nbeal2(-/-) murine model of GPS and demonstrate that the lack of α-granules is due to their loss from platelets/mature megakaryocytes (MKs), and not by initial impaired formation. We show that the lack of Nbeal2 confers a proinflammatory phenotype to the bone marrow MKs, which in combination with the loss of proteins from α-granules drives the development of bone marrow fibrosis. In addition, we demonstrate that α-granule deficiency impairs platelet function beyond their purely hemostatic role and that Nbeal2 deficiency has a protective effect against cancer metastasis.
Selo DaSilva