|
|
Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2001-12-0263.
Submitted December 21, 2001
Accepted April 15, 2002
BclxL Overexpression in Megakaryocytes Leads to Impaired Platelet Fragmentation
Yulia Kaluzhny, Yu Guangyao, Sun Shishinn, Paul A Toselli, Bernhard Nieswandt, Carl W Jackson, and Katya Ravid*
Biochemistry, Boston University School of Medicine, Boston, MA, USA
Whittaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA
Molecular Oncology, Witten/Herdecke University, Wuppertal, Germany
Biochemistry, Boston University School of Medicine, Boston, MA, USA; Experimental Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA
* Corresponding author; email: ravid{at}biochem.bumc.bu.edu.
Fragmentation of polyploid megakaryocytes into platelets has great relevance for blood homeostasis. Apoptotic cell death is a highly regulated genetic program, which has been observed in mature megakaryocytes fragmenting into platelets. The anti-apoptotic protein BclxL has been reported as upregulated during megakaryocytic differentiation in vitro, but absent during late megakaryopoiesis. Our study has focused on examining BclxL levels in megakaryocytes in vivo and in assessing the effect of its overexpression in transgenic mice (via the platelet factor four (PF4) promoter) on megakaryocyte development and platelet fragmentation. Interestingly, in the wild type and less in PF4-driven transgenic mice, BclxL was not detected in a fraction of the large mature megakaryocytes, suggesting a regulation on protein level. BclxL overexpression was associated with a moderate increase in megakaryocyte number, with no significant change in ploidy level or platelet counts. When the mice were challenged by induction of immune thrombocytopenia, the rate of platelet recovery was significantly slower in the transgenic mice as compared to control. Moreover, proplatelet formation in vitro by transgenic megakaryocytes was limited. In accordance, transgenic megakaryocytes displayed poorly developed platelet demarcation membranes and cell margin extensions. Our study indicates that regulated expression of BclxL in megakaryocytes is important for the development of cells with a high potential to fragment into platelets.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. E. Geddis
The regulation of proplatelet production
Haematologica,
June 1, 2009;
94(6):
756 - 759.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. O. Ciurea, D. Merchant, N. Mahmud, T. Ishii, Y. Zhao, W. Hu, E. Bruno, G. Barosi, M. Xu, and R. Hoffman
Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis
Blood,
August 1, 2007;
110(3):
986 - 993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. G. Nguyen, G. Yu, M. Makitalo, D. Yang, H.-X. Xie, M. R. Jones, and K. Ravid
Conditional overexpression of transgenes in megakaryocytes and platelets in vivo
Blood,
September 1, 2005;
106(5):
1559 - 1564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, Y. Nagata, G. Yu, H. G. Nguyen, M. R. Jones, P. Toselli, C. W. Jackson, M. Tatsuka, K. Todokoro, and K. Ravid
Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated expression
Blood,
May 15, 2004;
103(10):
3717 - 3726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Nagata, J. Yoshikawa, A. Hashimoto, M. Yamamoto, A. H. Payne, and K. Todokoro
Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol
Genes & Dev.,
December 1, 2003;
17(23):
2864 - 2869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
