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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4081-4091. Prepublished online as a Blood First Edition Paper on February 14, 2008; DOI 10.1182/blood-2007-09-113266. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-09-113266v1 111/8/4081    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gilles, L. Articles by Raslova, H. Search for Related Content PubMed PubMed Citation Articles by Gilles, L. Articles by Raslova, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 17, 2007 Accepted February 6, 2008 P19INK4D links endomitotic arrest and megakaryocyte maturation and is regulated by AML-1 Laure Gilles, Romain Guieze, Dominique Bluteau, Veronique Cordette-Lagarde, Catherine Lacout, Remi Favier, Frederic Larbret, Najet Debili, William Vainchenker, and Hana Raslova* Institut National de la Sante et de la Recherche Medicale (INSERM), U790, Villejuif, France Universite Paris VII, Villejuif, France Universite Paris XI, Villejuif, France Institut Gustave Roussy, IFR54, Villejuif, France Assistance Publique-Hopitaux de Paris, Hopital Trousseau, Service d'Hematologie biologique, Paris, France * Corresponding author; email: hraslova{at}igr.fr. The molecular mechanisms that regulate megakaryocyte (MK) ploidization are poorly understood. Using MK differentiation from primary human CD34+ cells, we observed that p19INK4D expression was increased both at the mRNA and protein levels during ploidization. p19INK4D knockdown led to a moderate increase (31.7±5%) in the mean ploidy of MLs suggesting a role of p19INK4D in the endomitotic arrest. This increase in ploidy was associated with a decrease in the more mature MK population (CD41highCD42high) at day 9 of culture, which was related to a delay in differentiation. Inversely, p19INK4D overexpression in CD34+ cells resulted in a decrease in mean ploidy level associated with an increase in CD41 and CD42 expression in each ploidy class. Confirming these in vitro results, bone marrow MKs from p19INK4D KO mice exhibited an increase in mean ploidy level from 18.7N (±0.58) to 52.7N (±12.3). Chromatin immunoprecipitation assays performed in human MKs revealed that AML-1 binds in vivo the p19INK4D promoter. Moreover, AML-1 inhibition led to the p19INK4D downregulation in human MKs. These results may explain the molecular link at the transcriptional level between the arrest of endomitosis and the acceleration of MK differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gilles, D. Bluteau, S. Boukour, Y. Chang, Y. Zhang, T. Robert, P. Dessen, N. Debili, O. A. Bernard, W. Vainchenker, et al. MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9 Blood, November 5, 2009; 114(19): 4221 - 4232. [Abstract] [Full Text] [PDF] O. Klimchenko, M. Mori, A. DiStefano, T. Langlois, F. Larbret, Y. Lecluse, O. Feraud, W. Vainchenker, F. Norol, and N. Debili A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis Blood, August 20, 2009; 114(8): 1506 - 1517. [Abstract] [Full Text] [PDF]

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