Journal
BLOOD
Volume 124, Issue 24, Pages 3624-3635Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-04-566760
Keywords
-
Categories
Funding
- British Heart Foundation [FS09/039, RG/09/12/28096]
- National Health Service: Blood and Transplant grant
- Wellcome Trust [WT098051]
- British Heart Foundation [FS/14/40/30921, FS/09/039/27788, RG/09/012/28096] Funding Source: researchfish
- Cancer Research UK [13031] Funding Source: researchfish
- National Institute for Health Research [RP-PG-0310-1002, NF-SI-0510-10214, NF-SI-0513-10151] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available