Aurora kinase a is required for hematopoiesis but is dispensable for murine megakaryocyte endomitosis and differentiation

Benjamin Goldenson, Gina Kirsammer, Monika J. Stankiewicz, Qiang Jeremy Wen, John D. Crispino*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Aurora kinase A (AURKA) is a therapeutic target in acute megakaryocytic leukemia. However, its requirement in normal hematopoiesis and megakaryocyte development has not been extensively characterized. Based on its role as a cell cycle regulator, we predicted that an Aurka deficiency would lead to severe abnormalities in all hematopoietic lineages. Herewereveal that loss of Aurka in hematopoietic cells causesprofound cell autonomous defects in the peripheral blood and bone marrow. Surprisingly, in contrast to the survival defects of nearly all hematopoietic lineages, deletion of Aurka was associated with increased differentiation andpolyploidization of megakaryocytes both in vivoandin vitro. Furthermore, in contrast to other cell types examined, megakaryocytes continued DNA synthesis after loss of Aurka. Thus, like other cell cycle regulators such as Aurkb and survivin, Aurka is required for hematopoiesis, but is dispensable for megakaryocyte endomitosis. Our work supports a growing body of evidence that the megakaryocyte endomitotic cell cycle differs significantly from the proliferative cell cycle.

Original languageEnglish (US)
Pages (from-to)2141-2150
Number of pages10
JournalBlood
Volume125
Issue number13
DOIs
StatePublished - Mar 26 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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