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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 10, 2007 Accepted September 24, 2008 Very late antigen-4 (VLA-4) function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia Pamela S. Becker*, Kenneth J. Kopecky, Adrianne N. Wilks, Sylvia Chien, John M. Harlan, Cheryl L. Willman, Stephen H Petersdorf, Derek L Stirewalt, Thalia Papayannopoulou, and Frederick R. Appelbaum Division of Hematology, University of Washington, Seattle, WA, United States Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM, United States Division of Medical Oncology, University of Washington, Seatlle, WA, United States Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States * Corresponding author; email: pbecker{at}u.washington.edu. Adhesion of acute myeloid leukemia (AML) blasts in the bone marrow (BM) microenvironment confers protection from chemotherapy-induced apoptosis. One mechanism for retention of blasts within the BM is adhesion via VLA-4, the 41 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 1 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 = 0.033). Estimated 5-yr OS was 31% (95% CI 14-48%) in 30 patients with sVCAM-1 binding 40%, compared to 10% (CI 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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