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This Article Full Text Full Text (PDF) 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 Möhle, R. Articles by Kanz, L. Search for Related Content PubMed PubMed Citation Articles by Möhle, R. Articles by Kanz, L. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  The Chemokine Receptor CXCR-4 Is Expressed on CD34+ Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1 Robert Möhle, Frank Bautz, Shahin Rafii, Malcolm A.S. Moore, Wolfram Brugger, and Lothar Kanz From the Department of Medicine II, University of Tübingen, Tübingen, Germany; New York Hospital Cornell Medical Center, Division of Hematology and Oncology, New York, NY; and the Laboratory of Developmental Hematopoiesis, Sloan-Kettering Institute, New York, NY. The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1-deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1-induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38 and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1-induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1 induced migration of CXCR-4-positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+ cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells. Blood, Vol. 91 No. 12 (June 15), 1998: pp. 4523-4530 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. H. Seeger, T. Rasper, M. Koyanagi, H. Fox, A. M. Zeiher, and S. 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Oda, H. Nakata, Y. Shozaki, T. Kozasa, and K. Todokoro A novel regulator of G-protein signaling bearing GAP activity for G{alpha}i and G{alpha}q in megakaryocytes Blood, May 15, 2001; 97(10): 3051 - 3060. [Abstract] [Full Text] [PDF] O. Kollet, A. Spiegel, A. Peled, I. Petit, T. Byk, R. Hershkoviz, E. Guetta, G. Barkai, A. Nagler, and T. Lapidot Rapid and efficient homing of human CD34+CD38{-}/lowCXCR4+ stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2mnull mice Blood, May 15, 2001; 97(10): 3283 - 3291. [Abstract] [Full Text] [PDF] F. Prosper and C. M. Verfaillie Regulation of hematopoiesis through adhesion receptors J. Leukoc. Biol., March 1, 2001; 69(3): 307 - 316. [Abstract] [Full Text] C. Voermans, M. L. K. Kooi, S. Rodenhuis, H. van der Lelie, C. E. van der Schoot, and W. R. Gerritsen In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation Blood, February 1, 2001; 97(3): 799 - 804. [Abstract] [Full Text] [PDF] F. Sanz-Rodriguez, A. Hidalgo, and J. Teixido Chemokine stromal cell-derived factor-1{alpha} modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1 Blood, January 15, 2001; 97(2): 346 - 351. [Abstract] [Full Text] [PDF] M. Majka, A. Janowska-Wieczorek, J. Ratajczak, M. A. Kowalska, G. Vilaire, Z. K. Pan, M. Honczarenko, L. A. Marquez, M. Poncz, and M. Z. Ratajczak Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis Blood, December 15, 2000; 96(13): 4142 - 4151. [Abstract] [Full Text] [PDF] J.-F. Wang, I.-W. Park, and J. E. Groopman Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C Blood, April 15, 2000; 95(8): 2505 - 2513. [Abstract] [Full Text] [PDF] J.-J. Lataillade, D. Clay, C. Dupuy, S. Rigal, C. Jasmin, P. Bourin, and M.-C. L. Bousse-Kerdiles Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival Blood, February 1, 2000; 95(3): 756 - 768. [Abstract] [Full Text] [PDF] K. Hodohara, N. Fujii, N. Yamamoto, and K. Kaushansky Stromal cell-derived factor-1 (SDF-1) acts together with thrombopoietin to enhance the development of megakaryocytic progenitor cells (CFU-MK) Blood, February 1, 2000; 95(3): 769 - 775. [Abstract] [Full Text] [PDF] A. J. Naiyer, D.-Y. Jo, J. Ahn, R. Mohle, M. Peichev, G. Lam, R. L. Silverstein, M. A.S. Moore, and S. 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Clarke Molecular Cloning and Characterization of a Novel Regulator of G-protein Signaling from Mouse Hematopoietic Stem Cells J. Biol. Chem., January 5, 2001; 276(2): 915 - 923. [Abstract] [Full Text] [PDF] M. A. Simpson, J. Reiland, S. R. Burger, L. T. Furcht, A. P. Spicer, T. R. Oegema Jr., and J. B. McCarthy Hyaluronan Synthase Elevation in Metastatic Prostate Carcinoma Cells Correlates with Hyaluronan Surface Retention, a Prerequisite for Rapid Adhesion to Bone Marrow Endothelial Cells J. Biol. Chem., May 18, 2001; 276(21): 17949 - 17957. [Abstract] [Full Text] [PDF]

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