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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3286-3294. Prepublished online as a Blood First Edition Paper on December 23, 2004; DOI 10.1182/blood-2004-06-2101. This Article Full Text (PDF) All Versions of this Article: 2004-06-2101v1 105/8/3286    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 Zhang, H. Articles by Batuman, O. A Search for Related Content PubMed PubMed Citation Articles by Zhang, H. Articles by Batuman, O. A Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 4, 2004 Accepted December 15, 2004 Circulating endothelial progenitor cells in multiple myeloma: implications and significance Hong Zhang, Varsha Vakil, Marc Braunstein, Eric L Smith, Justin Maroney, Laurie Chen, Kezhi Dai, James R Berenson, M M Hussain, Uwe Klueppelberg, Allen J Norin, Hasan O Akman, Tayfun Ozcelik, and Olcay A Batuman* Division of Hematology/Oncology, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, USA Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY, USA Institute for Myeloma & Bone Cancer Research, UCLA School of Medicine, Los Angeles, CA, USA Transplant Immunology & Immunogenetics Laboratory, State University of New York Downstate Medical Center, Brooklyn, NY, USA Department of Molecular Biology and Genetics, Ayhan Sahenk Foundation and Bilkent University, Bilkent, Ankara, Turkey * Corresponding author; email: obatuman{at}downstate.edu. Angiogenesis governs the progression of multiple myeloma (MM). Circulating endothelial cells (CECs) contribute to angiogenesis and comprise mature ECs and endothelial progenitor cells (EPCs). The present study sought to characterize CECs and their relation to disease activity and therapeutic response in thirty-one consecutive MM patients. CECs, identified as CD34+/CD146+/CD105+/CD11b- cells, were 6-fold higher in patients compared to controls, and correlated positively with serum M protein and 2-microglobulin. Circulating EPCs displayed late colony formation/outgrowth and capillary-like network formation on Matrigel; these processes were inhibited after effective thalidomide treatment. Co-expression of vascular endothelial growth factor receptor-2 (KDR) and CD133 characterized EPCs in MM, and KDR mRNA elevations correlated with M protein levels. In vitro exposure of ECs to thalidomide or its derivative CC-5013 inhibited gene expression of the receptors for transforming growth factor- and thrombin. Thus, elevated levels of CECs and EPCs covary with disease activity and response to thalidomide, underscoring the angiogenic aspect of MM and suggesting that angioblast-like EPCs are a pathogenic biomarker and a rational treatment target in MM. The results also highlight the anti-angiogenic properties of thalidomide and CC-5013, and further elucidate possible mechanisms of their effectiveness against MM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Another dangerous traveler in myeloma blood? Joachim Kienast and Wolfgang E. Berdel Blood 2005 105: 3009-3010. [Full Text] [PDF] This article has been cited by other articles: A. Zampetaki, J. P. Kirton, and Q. Xu Vascular repair by endothelial progenitor cells Cardiovasc Res, June 1, 2008; 78(3): 413 - 421. 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