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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2688-2692. Prepublished online as a Blood First Edition Paper on July 7, 2005; DOI 10.1182/blood-2005-03-1240. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1240v1 106/8/2688    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 Catlin, S. N. Articles by Abkowitz, J. L. Search for Related Content PubMed PubMed Citation Articles by Catlin, S. N. Articles by Abkowitz, J. L. Related Collections Hematopoiesis and Stem Cells Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The kinetics of clonal dominance in myeloproliferative disorders Sandra N. Catlin, Peter Guttorp, and Janis L. Abkowitz From the Department of Mathematical Sciences, University of Nevada, Las Vegas, NV; and the Departments of Statistics and Medicine, University of Washington, Seattle, WA. To study clonal evolution in myeloproliferative disorders, we used stochastic models of hematopoiesis for mouse and cat, species for which the in vivo kinetics of hematopoietic stem cells (HSCs) have been experimentally defined. We determined the consequence if 1 HSC became able to survive without the support of a microenvironmental niche while the rest of its behavior did not change. Neoplastic cells persisted and dominated hematopoiesis in 14% of mice and 17% of cats, requiring mean times of 2.5 ± 0.5 and 7.0 ± 1.2 years, respectively (n = 1000 simulations/species). In both species, when the number of neoplastic HSCs exceeded 0.5% of all HSCs, clonal dominance was inevitable. Our results can explain the absence of clonal myeloproliferative disorders in mice (lifetime, 2 years), are consistent with clinical observations in cats, and provide insight into the progression of chronic myelogenous leukemia (CML) in humans. They also demonstrate that competition for microenvironmental support can lead to the suppression of normal hematopoiesis as neoplasia evolves. Toxic or immunologic suppression of normal HSCs is not required. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Antonioli, P. Guglielmelli, G. Poli, V. Santini, A. Bosi, and A. M. Vannucchi Polycythemia vera following autologous transplantation for AML: insights on the kinetics of JAK2V617F clonal dominance Blood, December 15, 2007; 110(13): 4620 - 4621. [Full Text] [PDF] J. V. Lopes, J. M. Pacheco, and D. Dingli Acquired hematopoietic stem-cell disorders and mammalian size Blood, December 1, 2007; 110(12): 4120 - 4122. [Abstract] [Full Text] [PDF] P. J. Campbell and A. R. Green Methuselah conundrum: MPDs in the elderly Blood, September 1, 2007; 110(5): 1409 - 1409. [Full Text] [PDF] M. A. Vickers JAK2 617V>F positive polycythemia rubra vera maintained by approximately 18 stochastic stem-cell divisions per year, explaining age of onset by a single rate-limiting mutation Blood, September 1, 2007; 110(5): 1675 - 1680. [Abstract] [Full Text] [PDF] F. Passamonti, E. Rumi, D. Pietra, M. G. D. Porta, E. Boveri, C. Pascutto, L. Vanelli, L. Arcaini, S. Burcheri, L. Malcovati, et al. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders Blood, May 1, 2006; 107(9): 3676 - 3682. [Abstract] [Full Text] [PDF]

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