SEARCH:   Advanced

Blood, 1 November 2007, Vol. 110, No. 9, pp. 3334-3344. Prepublished online as a Blood First Edition Paper on August 13, 2007; DOI 10.1182/blood-2007-01-068122. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2007-01-068122v1 blood-2007-01-068122v2 110/9/3334    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 Wang, L. Articles by Gibson, L. F. Search for Related Content PubMed PubMed Citation Articles by Wang, L. Articles by Gibson, L. F. Related Collections Hematopoiesis and Stem Cells Neoplasia Cell Adhesion and Motility Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Ph+/VE-cadherin+ identifies a stem cell–like population of acute lymphoblastic leukemia sustained by bone marrow niche cells Lin Wang1, Heather O'Leary2, James Fortney1, and Laura F. Gibson13 1 Department of Pediatrics, 2 Department of Microbiology and Immunology, and 3 Mary Babb Randolph Cancer Center, West Virginia University, School of Medicine, Morgantown Although leukemic stem cells (LSCs) show a symbiotic relationship with bone marrow microenvironmental niches, the mechanism by which the marrow microenvironment contributes to self-renewal and proliferation of LSCs remains elusive. In the present study, we identified a unique subpopulation of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) cells coexpressing markers of endothelial cells (including VE-cadherin, PECAM-1, and Flk-1) and committed B-lineage progenitors. After long-term coculture with bone marrow stromal cells, tumor cells formed hematopoietic colonies and cords, expressed early stem- cell markers, and showed endothelial sprouting. Gene expression profiles of LSCs were altered in the presence of stromal cell contact. Stromal cell contact promoted leukemic cell VE-cadherin expression, stabilized β-catenin, and up-regulated Bcr-abl fusion gene expression. Our study indicates that these specific tumor cells are uniquely positioned to respond to microenvironment-derived self-renewing and proliferative cues. Ph+/VE-cadherin+ tumor subpopulation circumvents the requirement of exogenous Wnt signaling for self-renewal through stromal cell support of leukemic cell VE-cadherin expression and up-regulated Bcr-abl tyrosine kinase activity. These data suggest that strategies targeting signals in the marrow microenvironment that amplify the Bcr-abl/VE-cadherin/β-catenin axis may have utility in sensitizing drug-resistant leukemic stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Sozer, M. I. Fiel, T. Schiano, M. Xu, J. Mascarenhas, and R. Hoffman The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome Blood, May 21, 2009; 113(21): 5246 - 5249. [Abstract] [Full Text] [PDF] R. Majeti, M. W. Becker, Q. Tian, T.-L. M. Lee, X. Yan, R. Liu, J.-H. Chiang, L. Hood, M. F. Clarke, and I. L. Weissman Dysregulated gene expression networks in human acute myelogenous leukemia stem cells PNAS, March 3, 2009; 106(9): 3396 - 3401. [Abstract] [Full Text] [PDF] I. Samudio, M. Fiegl, T. McQueen, K. Clise-Dwyer, and M. Andreeff The Warburg Effect in Leukemia-Stroma Cocultures Is Mediated by Mitochondrial Uncoupling Associated with Uncoupling Protein 2 Activation Cancer Res., July 1, 2008; 68(13): 5198 - 5205. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020