Experimental Hematology
Volume 34, Issue 8 , Pages 1052-1059 , August 2006

The CXCR4 antagonist AMD3100 releases a subset of G-CSF-primed peripheral blood progenitor cells with specific gene expression characteristics

  • Stefan Fruehauf

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • Corresponding Author InformationOffprint requests to: Stefan Fruehauf, M.D., Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    • ,
  • Timon Seeger

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Patrick Maier

      Affiliations

    • Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Heidelberg, Germany
    • ,
  • Li Li

      Affiliations

    • Anormed Inc, Langley, Canada
    • ,
  • Stephan Weinhardt

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Stephanie Laufs

      Affiliations

    • Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Heidelberg, Germany
    • ,
  • Wolfgang Wagner

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Volker Eckstein

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Gary Bridger

      Affiliations

    • Research Program Innovative Cancer Diagnostics and Therapy, German Cancer Research Center (DKFZ), Heidelberg, Germany
    • ,
  • Gary Calandra

      Affiliations

    • Research Program Innovative Cancer Diagnostics and Therapy, German Cancer Research Center (DKFZ), Heidelberg, Germany
    • ,
  • Frederick Wenz

      Affiliations

    • Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Heidelberg, Germany
    • ,
  • W. Jens Zeller

      Affiliations

    • Research Program Innovative Cancer Diagnostics and Therapy, German Cancer Research Center (DKFZ), Heidelberg, Germany
    • ,
  • Hartmut Goldschmidt

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Anthony D. Ho

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

References 

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  2. Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999;283:845–848
  3. Lapidot T, Dar A, Kollet O. How do stem cells find their way home?. Blood. 2005;106:1901–1910
  4. Liles WC, Broxmeyer HE, Rodger E, et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood. 2003;102:2728–2730
  5. Broxmeyer HE, Orschell CM, Clapp DW, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med. 2005;201:1307–1318
  6. Flomenberg N, Devine SM, Dipersio JF, et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005;106:1867–1874
  7. Fruehauf S, Seeger T, Bridger G, Calandra G, Goldschmidt H, Ho AD. The CXCR4 antagonist AMD3100 mobilizes a more primitive subset of CD34+ cells than G-CSF [abstract]. Blood (ASH Annual Meeting Abstracts), Nov 2005;106:1969.
  8. Fruehauf S, Seeger T, Topaly J, et al. The CXCR4-antagonist AMD3100 augments the number of mobilized peripheral blood progenitor cells (PBPC) when added to a G-CSF standard mobilization regime and AMD3100-mobilized PBPC result in rapid hematopoietic reconstitution after autologous transplantation [abstract]. Blood (ASH Annual Meeting Abstracts), Nov 2005;106:1961.
  9. Steidl U, Kronenwett R, Rohr UP, et al. Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells. Blood. 2002;99:2037–2044
  10. Wagner W, Ansorge A, Wirkner U, et al. Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis. Blood. 2004;104:675–686
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  12. Wagner W, Saffrich R, Wirkner U, et al. Hematopoietic progenitor cells and their niche—initial behavioral and genetic alterations leading to asymmetric division. Stem Cells. 2005;23:1180–1191
  13. Maier P, Fleckenstein K, Li L, et al. Gene therapeutic overexpression of MDR1 differentially regulates genes involved in detoxification and apoptosis and confers radioprotection. Radiat Res. In press.
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  15. Larochelle A, Krouse A, Metzger M, et al. AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates. Blood. 2006;107:3772–3778
  16. Fruehauf S, Breems DA, Kaan-Shanzer S, et al. Frequency analysis of multidrug resistance-1 gene transfer into human primitive hematopoietic progenitor cells using the cobblestone area-forming cell assay and detection of vector-mediated P-glycoprotein expression by rhodamine-123. Hum Gene Ther. 1996;7:1219–1231
  17. Ota T, Fujii M, Sugizaki K, et al. Targets of transcriptional regulation by two distinct type I receptors for transforming growth factor-beta in human umbilical vein endothelial cells. J Cell Physiol. 2002;193:299–318
  18. Moriuchi M, Moriuchi H, Margolis DM, Fauci AS. USF/c-Myc enhances, while Yin-Yang 1 suppresses the promoter activity of CXCR4, a coreceptor for HIV-1 entry. J Immunol. 1999;162:5986–5992
  19. Luo Y, Cai J, Xue H, Miura T, Rao MS. Functional SDF1 alpha/CXCR4 signaling in the developing spinal cord. J Neurochem. 2005;93:452–462
  20. Tan X, Sanders P, Bolado J, Whitney M. Integration of G-protein coupled receptor signaling pathways for activation of a transcription factor (EGR-3). Genomics Proteomics Bioinformatics. 2003;1:173–179
  21. Hammer M, Mages J, Dietrich H, et al. Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. Eur J Immunol. 2005;35:2991–3001

PII: S0301-472X(06)00378-X

doi: 10.1016/j.exphem.2006.06.003

Experimental Hematology
Volume 34, Issue 8 , Pages 1052-1059 , August 2006

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