| First Author | Guerrero JA | Year | 2014 |
| Journal | Blood | Volume | 124 |
| Issue | 24 | Pages | 3624-35 |
| PubMed ID | 25258341 | Mgi Jnum | J:220801 |
| Mgi Id | MGI:5636146 | Doi | 10.1182/blood-2014-04-566760 |
| Citation | Guerrero JA, et al. (2014) Gray platelet syndrome: proinflammatory megakaryocytes and alpha-granule loss cause myelofibrosis and confer metastasis resistance in mice. Blood 124(24):3624-35 |
| abstractText | 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 alpha-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 alpha-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 alpha-granules drives the development of bone marrow fibrosis. In addition, we demonstrate that alpha-granule deficiency impairs platelet function beyond their purely hemostatic role and that Nbeal2 deficiency has a protective effect against cancer metastasis. |
