title: Aurora kinase A is required for hematopoiesis but is dispensable for murine megakaryocyte endomitosis and differentiation.
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. Here we reveal that loss of Aurka in hematopoietic cells causes profound 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 and polyploidization of megakaryocytes both in vivo and in 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.
authors: Division of Hematology/Oncology, Northwestern University, Chicago, IL.
authors: Benjamin
authors: B
authors: Goldenson
authors: Division of Hematology/Oncology, Northwestern University, Chicago, IL.
authors: Gina
authors: G
authors: Kirsammer
authors: Division of Hematology/Oncology, Northwestern University, Chicago, IL.
authors: Monika J
authors: MJ
authors: Stankiewicz
authors: Division of Hematology/Oncology, Northwestern University, Chicago, IL.
authors: Qiang Jeremy
authors: QJ
authors: Wen
authors: Division of Hematology/Oncology, Northwestern University, Chicago, IL.
authors: John D
authors: JD
authors: Crispino
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D064096:Aurora Kinase A / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000235:genetics*; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics*; D011123:Polyploidy; D034061:Thrombopoiesis / Q000235:genetics
chemical_list: C576918:Aurka protein, mouse; D064096:Aurora Kinase A