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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2900-2907. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-1891. This Article Full Text (PDF) All Versions of this Article: 2003-06-1891v1 103/8/2900    most recent Alert me when this article is cited Alert me if a correction is posted 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 Spiegel, A. Articles by Lapidot, T. Search for Related Content PubMed PubMed Citation Articles by Spiegel, A. Articles by Lapidot, T. Social Bookmarking                   What's this? Submitted June 12, 2003 Accepted November 5, 2003 Unique SDF-1 induced activation of human precursor-B ALL cells due to altered CXCR4 expression and signaling Asaf Spiegel, Orit Kollet, Amnon Peled, Loya Abel, Arnon Nagler, Bella Bielorai, Gideon Rechavi, Josef Vormoor, and Tsvee Lapidot* Department of Immunology, Weizmann Institute of Science, Rehovot, Israel Gene Therapy Institute, Hadassah University Hospital, Jerusalem, Israel Department of Bone Marrow Transplantation, Sheba Medical Center, Ramat-Gan, Israel Department of Pediatric Hemato-Oncology, Sheba Medical Center, Ramat-Gan, Israel Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel Department of Pediatric Hematology and Oncology, University Children's Hospital, Meunster, Germany * Corresponding author; email: Tsvee.Lapidot{at}weizmann.ac.il. The mechanisms governing migration and extramedullary dissemination of leukemic cells remain obscure. In this study the migration and in vivo homing to the bone marrow of NOD/SCID mice injected with human precursor-B ALL cells in comparison to normal CD34+ progenitors (both cord blood and mobilized peripheral blood) was investigated. Though migration and homing of both cell populations was SDF-1/CXCR4 dependent, major differences in receptor expression as well as the migratory capacity towards various concentrations of SDF-1 were found. Furthermore, unlike normal CD34+ progenitors, in vivo homing of the leukemic cells was superior when recipient NOD/SCID mice were not irradiated prior to transplantation. In addition, we report differences in the adhesion molecules activated upon SDF-1 stimulation, documenting a major role for VLA-4, but not VLA-5 and LFA-1, in homing of precursor-B ALL cells. Interestingly, Toxin-B and pertusis toxin inhibited the homing of the leukemic cells, but not that of normal CD34+ progenitors or normal CD10+/CD19+ precursor-B cells, revealing differences in CXCR4 signaling pathways that are based on changes acquired by the leukemic cells. Altogether, our data provides new insights into different SDF-1-induced signaling, activation and consequent motility between normal CD34+ and precursor-B ALL progenitors, which may lead to improved clinical protocols. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Wang, W. Zhang, T. Ishii, S. Sozer, J. Wang, M. Xu, and R. Hoffman Correction of the Abnormal Trafficking of Primary Myelofibrosis CD34+ Cells by Treatment with Chromatin-Modifying Agents Cancer Res., October 1, 2009; 69(19): 7612 - 7618. [Abstract] [Full Text] [PDF] T. N. Hartmann, V. Grabovsky, W. Wang, P. Desch, G. Rubenzer, S. Wollner, I. Binsky, A. 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