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Blood, 15 January 2004, Vol. 103, No. 2, pp. 523-529. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-05-1535. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1535v1 103/2/523    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 Bartolovic, K. Articles by Brümmendorf, T. H. Search for Related Content PubMed PubMed Citation Articles by Bartolovic, K. Articles by Brümmendorf, T. H. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Inhibitory effect of imatinib on normal progenitor cells in vitro Kerol Bartolovic, Stefan Balabanov, Ulrike Hartmann, Martina Komor, Andreas M. Boehmler, Hans-Jörg Bühring, Robert Möhle, Dieter Hoelzer, Lothar Kanz, Wolf-Karsten Hofmann, and Tim H. Brümmendorf From the Department of Hematology and Oncology, University Medical Center, Tübingen, Germany; and Department of Hematology and Oncology, University Medical Center, Frankfurt/Main, Germany. Imatinib is a novel tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome–positive leukemias and other malignancies. Side effects are mostly moderate; however, a dose-dependent hematologic toxicity affecting all hematopoietic lineages is observed clinically. The aim of this study was to investigate the effect of imatinib on normal hematopoietic stem and progenitor cells in vitro. A dose-dependent decrease in proliferation potential was found when CD34+ cells were expanded in serum-free medium supplemented with 6 growth factors and imatinib. Functionally, a decrease in colony-forming capacity was observed under increasing doses of imatinib. However, no such effect on more primitive cobblestone area–forming cells was detectable. Both withdrawal of stem cell factor from our expansion cultures or functional inhibition of c-kit led to a similar degree of inhibition of expansion, whereas the effect of imatinib was substantially greater at all dose levels tested. These data suggest a significant inhibitory effect of imatinib on normal CD34+ progenitor (but not stem) cells that is largely independent of c-kit signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Gontarewicz, S. Balabanov, G. Keller, R. Colombo, A. Graziano, E. Pesenti, D. Benten, C. Bokemeyer, W. Fiedler, J. Moll, et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I Blood, April 15, 2008; 111(8): 4355 - 4364. [Abstract] [Full Text] [PDF] M. Buitenhuis, L. P. Verhagen, J. Cools, and P. J. Coffer Molecular Mechanisms Underlying FIP1L1-PDGFRA-Mediated Myeloproliferation Cancer Res., April 15, 2007; 67(8): 3759 - 3766. [Abstract] [Full Text] [PDF] S. Balabanov, A. Gontarewicz, P. Ziegler, U. Hartmann, W. Kammer, M. Copland, U. Brassat, M. Priemer, I. Hauber, T. Wilhelm, et al. Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic target in BCR-ABL-positive leukemias identified by a proteomics approach Blood, February 15, 2007; 109(4): 1701 - 1711. 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