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Blood, 15 July 2004, Vol. 104, No. 2, pp. 550-557. Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2004-02-0566. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0566v1 104/2/550    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 Rombouts, E. J. C. Articles by Ploemacher, R. E. Search for Related Content PubMed PubMed Citation Articles by Rombouts, E. J. C. Articles by Ploemacher, R. E. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Gene Expression Free Research Articles Chemokines, Cytokines, and Interleukins Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia Elwin J. C. Rombouts, Biljana Pavic, Bob Löwenberg, and Rob E. Ploemacher From the Department of Haematology, Erasmus Medical Center, Rotterdam, The Netherlands. Recently it was shown that, analogous to normal hematopoietic cells, the level of CXC chemokine receptor 4 (CXCR-4) expression on acute myeloid leukemia (AML) cells correlates with stromal cell derived factor-1 alpha (SDF-1)-induced chemotaxis. As we speculated that an anomalous organ distribution of AML cells could affect cell survival and thus result in an altered fraction surviving chemotherapy, we examined a possible correlation between patient prognosis and CXCR-4 expression in AML patients. We found that patients with a high CXCR-4 expression in the CD34+ subset had a significantly reduced survival and a higher probability of relapse, resulting in a median relapse-free survival (RFS) of only 8.3 months. CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) AML than in Flt3/wild-type (wt) AML. Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analyzed in conjunction with the expression of CXCR-4 in the CD34+ subset, suggesting that the poor prognosis of Flt3/ITD AML might be subordinate to the increased CXCR-4 expression. Using a granulocyte colony-stimulating factor receptor (G-CSF-R)-expressing 32D cell line, we observed that SDF-1/CXCR-4 interaction is required for the survival of myeloid differentiating cells, and it also induces a block in G-CSF-induced myeloid differentiation. These data suggest that the SDF-1/CXCR-4 axis may influence therapy responsiveness and defines unfavorable prognosis in AML. (Blood. 2004;104:550-557) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CXCR-4: homing in on Flt3 Mark Levis Blood 2004 104: 303-304. [Full Text] [PDF] This article has been cited by other articles: R. Grundler, L. Brault, C. Gasser, A. N. Bullock, T. Dechow, S. Woetzel, V. Pogacic, A. Villa, S. Ehret, G. Berridge, et al. Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration J. Exp. Med., August 31, 2009; 206(9): 1957 - 1970. 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Gjertsen Subclassification of patients with acute myelogenous leukemia based on chemokine responsiveness and constitutive chemokine release by their leukemic cells Haematologica, March 1, 2007; 92(3): 332 - 341. [Abstract] [Full Text] [PDF] A. C. Spoo, M. Lubbert, W. G. Wierda, and J. A. Burger CXCR4 is a prognostic marker in acute myelogenous leukemia Blood, January 15, 2007; 109(2): 786 - 791. [Abstract] [Full Text] [PDF] A. Kalinkovich, S. Tavor, A. Avigdor, J. Kahn, A. Brill, I. Petit, P. Goichberg, M. Tesio, N. Netzer, E. Naparstek, et al. Functional CXCR4-Expressing Microparticles and SDF-1 Correlate with Circulating Acute Myelogenous Leukemia Cells. Cancer Res., November 15, 2006; 66(22): 11013 - 11020. [Abstract] [Full Text] [PDF] J. A. Burger and T. J. Kipps CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment Blood, March 1, 2006; 107(5): 1761 - 1767. [Abstract] [Full Text] [PDF] S. Tavor, I. Petit, S. Porozov, P. Goichberg, A. Avigdor, S. 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Gorlick Messenger RNA Expression Levels of CXCR4 Correlate with Metastatic Behavior and Outcome in Patients with Osteosarcoma Clin. Cancer Res., April 1, 2005; 11(7): 2561 - 2567. [Abstract] [Full Text] [PDF] K. W. H. Yee, M. Schittenhelm, A.-M. O'Farrell, A. R. Town, L. McGreevey, T. Bainbridge, J. M. Cherrington, and M. C. Heinrich Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells Blood, December 15, 2004; 104(13): 4202 - 4209. [Abstract] [Full Text] [PDF] G. Monaco, J. W. Belmont, M. Konopleva, M. Andreeff, S. Tavor, I. Petit, O. Kollet, and T. Lapidot Correlation between CXCR4 and Homing or Engraftment of Acute Myelogenous Leukemia Cancer Res., September 15, 2004; 64(18): 6832 - 6833. [Full Text] [PDF]

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