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Blood, 22 January 2009, Vol. 113, No. 4, pp. 866-874. Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2007-12-124818. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-12-124818v1 113/4/866    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 Becker, P. S. Articles by Appelbaum, F. R. Search for Related Content PubMed PubMed Citation Articles by Becker, P. S. Articles by Appelbaum, F. R. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia Pamela S. Becker1, Kenneth J. Kopecky2, Adrianne N. Wilks1, Sylvia Chien1, John M. Harlan1, Cheryl L. Willman3, Stephen H. Petersdorf4, Derek L. Stirewalt5, Thalia Papayannopoulou1, and Frederick R. Appelbaum5 1 Division of Hematology, University of Washington, Seattle; 2 Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; 3 Cancer Research and Treatment Center, University of New Mexico, Albuquerque; 4 Division of Medical Oncology, University of Washington, Seattle; and 5 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Adhesion of acute myeloid leukemia (AML) blasts in the bone marrow microenvironment confers protection from chemotherapy-induced apoptosis. One mechanism for retention of blasts within the bone marrow is adhesion via very late antigen-4 (VLA-4), the 4β1 integrin heterodimer that binds to its main ligands, fibronectin, and vascular cell adhesion molecule-1 (VCAM-1). To examine the relationship of functional expression of VLA-4 to prognosis in AML, we studied marrow samples from 175 adult AML patients who underwent induction chemotherapy with anthracycline and cytarabine on Southwest Oncology Group trials. The studies included flow cytometry and functional in vitro assays for ligand binding and maximal β1 activation. VLA-4 expression varied widely, with mean expression 60.6% for 4, and was not significantly associated with response to chemotherapy, relapse-free, or overall survival (OS). However, increased binding of soluble VCAM-1 via VLA-4 was significantly associated with longer OS, corrected for age (P = .033). Estimated 5-year OS was 31% (95% confidence interval, 14%-48%) in 30 patients with soluble VCAM-1 binding greater than or equal to 40%, compared with 10% (confidence interval, 3%-17%) in 72 patients with lower binding. Adhesion and migratory properties of AML blasts thus appear to influence chemosensitivity and therefore may be therapeutic targets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Stefanidakis, K. Karjalainen, D. E. Jaalouk, C. G. Gahmberg, S. O'Brien, R. Pasqualini, W. Arap, and E. Koivunen Role of leukemia cell invadosome in extramedullary infiltration Blood, October 1, 2009; 114(14): 3008 - 3017. [Abstract] [Full Text] [PDF]

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