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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-01-0043. This Article Full Text (PDF) All Versions of this Article: 2002-01-0043v1 101/2/655    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 Schuster, C. Articles by Warmuth, M. Search for Related Content PubMed PubMed Citation Articles by Schuster, C. Articles by Warmuth, M. Social Bookmarking                   What's this? Submitted January 8, 2002 Accepted August 21, 2002 The effects of Bcr-Abl on C/EBP transcription factor regulation and neutrophilic differentiation are reverted by the Abl kinase inhibitor STI571 Christine Schuster, Karin Forster, Henning Dierks, Annika Elsaesser, Gerhard Behre, Nicola Simon, Susanne Danhauser-Riedl, Michael Hallek, and Markus Warmuth* Klinische Kooperationsgruppe Gentherapie, GSF - Forschungszentrum fuer Umwelt und Gesundheit, Muenchen, Germany Klinische Kooperationsgruppe Gentherapie, GSF - Forschungszentrum fuer Umwelt und Gesundheit, Muenchen, Germany; Medizinische Klinik III, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany Genzentrum, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany Klinische Kooperationsgruppe Leukaemien, GSF - Forschungszentrum fuer Umwelt und Gesundheit, Muenchen, Germany Medizinische Klinik III, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany; Medizinische Klinik III, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany; Genzentrum, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany Klinische Kooperationsgruppe Gentherapie, GSF - Forschungszentrum fuer Umwelt und Gesundheit, Muenchen, Germany; Medizinische Klinik III, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany; Genzentrum, Ludwig-Maximilians-Universitaet Muenchen, Muenchen, Germany * Corresponding author; email: warmuth{at}gsf.de. The clinical progression of chronic myeloid leukemia (CML) from chronic phase to blast crisis is characterized by the increasing failure of myeloid precursors to differentiate into mature granulocytes. This study was undertaken to investigate the influence of Bcr-Abl and of the small molecule Abl tyrosine kinase inhibitor STI571 on granulocyte-colony stimulating factor (G-CSF) induced neutrophilic differentiation. We show that differentiation of 32Dcl3 cells into mature granulocytes is accompanied by the increased expression of the antigens Mac-1 and Gr1, of the G-CSF receptor (G-CSF-R), of myeloid transcription factors (C/EBP, C/EBP and PU.1), and of the cyclin dependent kinase inhibitor p27Kip1. In 32Dcl3 cells transfected with the bcr-abl gene (32DBcr-Abl), G-CSF did not trigger granulocytic differentiation, nor the upregulation of C/EBP, C/EBP and the G-CSF-R. This could be correlated to a defect in c-Myc downregulation. In contrast, the upregulation of PU.1 and p27Kip1 by G-CSF was not affected by Bcr-Abl. Importantly, incubation of 32DBcr-Ablwt cells with the kinase inhibitor STI571 prior to G-CSF stimulation completely neutralized the effects of Bcr-Abl on granulocytic differentiation, and on C/EBP and C/EBP expression. Taken together, the results suggest that the Bcr-Abl kinase induces a reversible block of the granulocytic differentiation program in myeloid cells by disturbing regulation of hematopoietic transcription factors such as C/EBP and C/EBP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. S. Chang, R. Santhanam, R. Trotta, P. Neviani, A. M. Eiring, E. Briercheck, M. Ronchetti, D. C. Roy, B. Calabretta, M. A. Caligiuri, et al. 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