SEARCH:   Advanced

Blood, 15 October 2004, Vol. 104, No. 8, pp. 2291-2298. Prepublished online as a Blood First Edition Paper on June 1, 2004; DOI 10.1182/blood-2003-05-1745. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1745v1 104/8/2291    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Paulus, J.-M. Articles by Vainchenker, W. Search for Related Content PubMed PubMed Citation Articles by Paulus, J.-M. Articles by Vainchenker, W. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors Jean-Michel Paulus, Najet Debili, Frédéric Larbret, Jack Levin, and William Vainchenker From the Laboratory of Hematology, Hôpital du Sart Tilman, University of Liège, Liège, Belgium; the Institut National de la Santé et de la Recherche Médicale (INSERM) U362, Institut Gustave Roussy, Villejuif, France; and the Department of Laboratory Medicine, University of California School of Medicine, San Francisco. To assess the variation of thrombopoietin (TPO) responsiveness associated with megakaryocyte (MK) progenitor amplification, TPO dose-response curves were obtained for normal human, single-cell plated CD34+CD41+ cells. The number of MKs per well was determined in situ and expressed as number of doublings (NbD). Dose-response curves of the mean frequency of clones of each size versus log TPO concentration showed highly significant differences in the TPO concentration needed for half-maximum generation of clones of different sizes (TPO50): 1.89 ± 0.51 pg/mL for 1 MK clones; 7.75 ± 0.81 pg/mL for 2 to 3 MK clones; 38.5 ± 5.04 pg/mL for 4 to 7 MK clones, and 91.8 ± 16.0 pg/mL for 8 to 15 MK clones. These results were consistent with a prediction of the generation-age model, because the number of previous doublings in vivo was inversely correlated with the number of residual doublings in vitro. TPO responsiveness decreased in vitro by a factor of 3.5 per doubling, reflecting the recruitment of progressively more ancestral progenitors. In support of this hypothesis, the more mature CD34+CD41+CD42+ cell fraction had a lower TPO50 (P < .001), underwent fewer NbD (P < .001), and expressed a 2.8-fold greater median Mpl receptor density (P < .001) than the CD34+CD41+CD42– fraction. Progenitors that have completed their proliferative program have maximum factor responsiveness and are preferentially induced to terminal differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Chaligne, C. James, C. Tonetti, R. Besancenot, J. P. Le Couedic, F. Fava, F. Mazurier, I. Godin, K. Maloum, F. Larbret, et al. Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis Blood, November 15, 2007; 110(10): 3735 - 3743. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020