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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1017-1024.
Prepublished online as a Blood First Edition Paper on May 6, 2004; DOI 10.1182/blood-2004-02-0419.
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Submitted February 3, 2004
Accepted April 20, 2004
Megakaryocytes express functional aurora-B kinase in endomitosis
Amy E Geddis* and Ken Kaushansky
Medicine, University of California San Diego, San Diego, CA, USA
Pediatrics, University of California San Diego, San Diego, CA, USA
* Corresponding author; email: ageddis{at}ucsd.edu.
Endomitosis (EnM) in megakaryocytes (MKs) is characterized by abortion of mitosis in late anaphase and failure of cytokinesis; subsequent reinitiation of DNA synthesis results in polyploidy. Ablation of chromosomal passenger proteins including aurora-B kinase cause defects in late anaphase and cytokinesis in diploid cells; thus one hypothesis is that the expression or function of these proteins in polyploid MKs is abnormal. It has been reported that aurora kinase B mRNA is decreased in polyploid megakaryocytic cells, suggesting that deficiency of aurora-B kinase is responsible for EnM. We examined the localization of aurora-B kinase and additional members of the chromosomal passenger protein and aurora kinase families in MKs. We found that in EnM MKs 1) Aurora-B kinase is present and appropriately localized to centromeres in early EnM; 2) in low ploidy human MKs, centromeric localization of survivin and INCENP can also be demonstrated; 3) the function of aurora-B kinase, as measured by serine10 phosphorylation of histone H3, is intact; and 4) aurora-A kinase localizes appropriately to centrosomes in EnM. These results suggest that EnM MKs appropriately express functional aurora-B kinase and related proteins in early anaphase, making a simple deficiency of this protein an unlikely explanation for polyploidy in this cell type.

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