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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1238-1250. Prepublished online as a Blood First Edition Paper on April 9, 2007; DOI 10.1182/blood-2006-02-003772. This Article Full Text Full Text (PDF) Supplemental Methods All Versions of this Article: blood-2006-02-003772v1 110/4/1238    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 Pillozzi, S. Articles by Arcangeli, A. Search for Related Content PubMed PubMed Citation Articles by Pillozzi, S. Articles by Arcangeli, A. Related Collections Neoplasia Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA VEGFR-1 (FLT-1), β1 integrin, and hERG K+ channel for a macromolecular signaling complex in acute myeloid leukemia: role in cell migration and clinical outcome Serena Pillozzi1, Maria Felice Brizzi2, Pietro Antonio Bernabei3, Benedetta Bartolozzi3, Roberto Caporale4, Venere Basile3, Vieri Boddi6, Luigi Pegoraro2, Andrea Becchetti5, and Annarosa Arcangeli1 1 Department of Experimental Pathology and Oncology, University of Firenze, Firenze; 2 Department of Internal Medicine, University of Torino; 3 Azienda Ospedaliero Universitaria (A.O.U.). Hematology, Policlinico di Careggi, Firenze; 4 Azienda Ospedaliero Universitaria Careggi, Department of Laboratory Medicine, Firenze; 5 Department of Biotechnology and Biosciences, University of Milano Bicocca, Milano; and 6 Department of Public Health, Firenze, Italy Leukemia cell motility and transendothelial migration into extramedullary sites are regulated by angiogenic factors and are considered unfavorable prognostic factors in acute leukemias. We have studied cross talk among (1) the vascular endothelial growth factor receptor-1, FLT-1; (2) the human eag-related gene 1 (hERG1) K+ channels; and (3) integrin receptors in acute myeloid leukemia (AML) cells. FLT-1, hERG1, and the β1 integrin were found to form a macromolecular signaling complex. The latter mostly recruited the hERG1B isoform of hERG1 channels, and its assembly was necessary for FLT-1 signaling activation and AML cell migration. Both effects were inhibited when hERG1 channels were specifically blocked. A FLT-1/hERG1/β1 complex was also observed in primary AML blasts, obtained from a population of human patients. The co-expression of FLT-1 and hERG1 conferred a pro-migratory phenotype to AML blasts. Such a phenotype was also observed in vivo. The hERG1-positive blasts were more efficient in invading the peripheral circulation and the extramedullary sites after engraftment into immunodeficient mice. Moreover, hERG1 expression in leukemia patients correlated with a higher probability of relapse and shorter survival periods. We conclude that in AML, hERG1 channels mediate the FLT-1–dependent cell migration and invasion, and hence confer a greater malignancy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. B. Ganapathi, M. Kester, and K. S. 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