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Blood, 1 January 2008, Vol. 111, No. 1, pp. 359-368. Prepublished online as a Blood First Edition Paper on September 26, 2007; DOI 10.1182/blood-2006-11-060632. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-11-060632v1 111/1/359    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 Fuhler, G. M. Articles by Vellenga, E. Search for Related Content PubMed PubMed Citation Articles by Fuhler, G. M. Articles by Vellenga, E. Related Collections Cell Adhesion and Motility Cytoskeleton Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Reduced activation of protein kinase B, Rac, and F-actin polymerization contributes to an impairment of stromal cell–derived factor-1–induced migration of CD34+ cells from patients with myelodysplasia Gwenny M. Fuhler1,2, A. Lyndsay Drayer3, Sandra G. M. Olthof1, Jan Jacob Schuringa1,2, Paul J. Coffer4, and Edo Vellenga1 1 Division of Hematology, Department of Medicine, University Medical Center Groningen, Groningen; 2 University of Groningen, Groningen; 3 Sanquin Blood Bank North East Netherlands, Groningen; and 4 Department of Immunology, University Medical Center Utrecht, the Netherlands Patients with myelodysplasia (MDS) show a differentiation defect in the multipotent stem-cell compartment. An important factor in stem-cell differentiation is their proper localization within the bone marrow microenvironment, which is regulated by stromal cell–derived factor (SDF-1). We now show that SDF-1–induced migration of CD34+ progenitor cells from MDS patients is severely impaired. In addition, these cells show a reduced capacity to polymerize F-actin in response to SDF-1. We demonstrate a major role for Rac and phosphatidylinositol 3-kinase (PI3K) and a minor role for the extracellular signal-regulated kinase (ERK)1/2 signaling pathway in SDF-1–induced migration of normal CD34+ cells. Furthermore, SDF-1–stimulated activation of Rac and the PI3K target protein kinase B is impaired in CD34+ cells from MDS patients. Lentiviral transduction of MDS CD34+ cells with constitutive active Rac1V12 results in a partial restoration of F-actin polymerization in response to SDF-1. In addition, expression of constitutive active Rac increases the motility of MDS CD34+ cells in the absence of SDF-1, although the directional migration of cells toward this chemoattractant is not affected. Taken together, our results show a reduced migration of MDS CD34+ cells toward SDF-1, as a result of impaired activation of the PI3K and Rac pathways and a decreased F-actin polymerization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Urao, H. Inomata, M. Razvi, H. W. Kim, K. Wary, R. McKinney, T. Fukai, and M. Ushio-Fukai Role of Nox2-Based NADPH Oxidase in Bone Marrow and Progenitor Cell Function Involved in Neovascularization Induced by Hindlimb Ischemia Circ. Res., July 18, 2008; 103(2): 212 - 220. [Abstract] [Full Text] [PDF]

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