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Blood, 2 July 2009, Vol. 114, No. 1, pp. 153-156. Prepublished online as a Blood First Edition Paper on April 1, 2009; DOI 10.1182/blood-2008-11-190801.
Submitted November 20, 2008
Division of Hematology/Oncology, Northwestern University, Chicago, IL, United States * Corresponding author; email: j-crispino{at}northwestern.edu.
Survivin is a member of the chromosome passenger complex, which plays an important role in chromosome alignment, separation and cytokinesis. Although survivin is required for the proliferation and survival of hematopoietic stem and progenitor cells, the extent to which it is necessary for endomitosis of megakaryocytes remains controversial. To determine whether survivin is required for polyploidization, we analyzed mice with a megakaryocyte specific deletion. PF4-Cre/Survivinfl/fl mice harbored normal platelet counts with megakaryocytes that reached ploidy states comparable to those of control littermates. The CD41+ cells within these animals showed little excision but increased annexin V staining, implying that survivin is required for survival of megakaryocyte progenitors in vivo. In contrast, megakaryocytes in which survivin was excised ex vivo showed robust excision and an increased degree of polyploidization. These results demonstrate that survivin is necessary for survival of megakaryocyte progenitors, but not required for polyploidization of committed megakaryocytes.
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