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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0659. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-02-0659v1 101/1/259    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 Burchert, A. Articles by Neubauer, A. Search for Related Content PubMed PubMed Citation Articles by Burchert, A. Articles by Neubauer, A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 259-264 NEOPLASIA Interferon-, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia Andreas Burchert, Stefan Wölfl, Manuel Schmidt, Cornelia Brendel, Barbara Denecke, Dali Cai, Larissa Odyvanova, Tanja Lahaye, Martin C. Müller, Thomas Berg, Harald Gschaidmeier, Burghardt Wittig, Rüdiger Hehlmann, Andreas Hochhaus, and Andreas Neubauer From the Klinikum der Philipps Universität Marburg, Klinik für Hämatologie, Onkologie und Immunologie, Germany; Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin, Germany; Mologen, Berlin, Germany; Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, III Medizinische Klinik, Germany; Charité-Virchow Klinikum, Medizinische Klinik, Gastroenterologie-Hepatologie, Humboldt Universität, Berlin, Germany; and Novartis Pharma, Nuremberg, Germany. Chronic myeloid leukemia (CML) is a clonal disease of hematopoietic stem cells caused by a reciprocal translocation of the long arms of chromosomes 9 and 22. In human leukocyte antigen A*0201+ (HLA-A*0201+) individuals, response after interferon- (IFN-) was shown to be associated with the emergence of CML-specific cytotoxic T cells that recognize PR-1, a myeloblastin (MBN)-derived nonapeptide. In contrast, imatinib potently induces remissions from CML by specific inhibition of the ABL tyrosine kinase. Here, we explored molecular regulations associated with CML responses under different treatment forms using cDNA-array. Expression of MBN was found to be down-regulated in remission under imatinib therapy (0 of 7 MBN+ patients). In contrast, MBN transcription was readily detectable in the peripheral blood in 8 of 8 tested IFN- patients in complete remission (P = .0002). IFN--dependent MBN transcription was confirmed in vitro by stimulation of peripheral blood mononuclear cells (PBMCs) with IFN- and by IFN--mediated activation of the MBN promoter in reporter gene assays. Finally, with the use of HLA-A*0201-restricted, MBN-specific tetrameric complexes, it was demonstrated that all of 4 IFN--treated patients (100%), but only 2 of 11 imatinib patients (19%), in complete hematological or cytogenetic remission developed MBN-specific cytotoxic T cells (P = .011). Together, the induction of MBN expression by IFN-, but not imatinib, may contribute to the specific ability of IFN- to induce an MBN-specific T-cell response in CML patients. This also implies that the character of remissions achieved with either drug may not be equivalent and therefore a therapy modality combining IFN- and imatinib may be most effective. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Nardi, O. Naveiras, M. Azam, and G. Q. Daley ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the CCL6 and CCL9 chemokines Blood, April 16, 2009; 113(16): 3813 - 3820. [Abstract] [Full Text] [PDF] T. O'Hare and M. W. Deininger Toward a Cure For Chronic Myeloid Leukemia Clin. Cancer Res., December 15, 2008; 14(24): 7971 - 7974. [Full Text] [PDF] H.-J. 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	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020