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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 (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 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. Social Bookmarking                   What's this? Submitted February 28, 2002 Accepted June 12, 2002 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 Woelfl, Manuel Schmidt, Cornelia Brendel, Barbara Dennecke, Dali Cai, Larissa Odynova, Tanja Lahaye, Martin C Mueller, Thomas Berg, Harald Gschaidmeier, Burghardt Wittig, Ruediger Hehlmann, Andreas Hochhaus, and Andreas Neubauer* Haematologie, Onkologie, Immunologie, Universitaetsklinikum Marburg, Marburg, Germany Klinik fuer Innere Medizin, Friedrich Schiller Universitaet Jena, Jena, Germany Mologen GmbH, Berlin, Germany Medizinische Klinik III, Fakultaet fuer Klinische Medizin Mannheim der Universitaet Heidelberg, Mannheim, Germany Medizinische Klinik, Gastroenterologie, Hepatologie, Charite Virchow Klinikum der Humboldt Universitaet, Berlin, Germany Novartis Pharma GmbH, Nuernberg, Germany * Corresponding author; email: neubauer{at}mailer.uni-marburg.de. Chronic myeloid leukemia (CML) is a clonal disease of hematopoietic stem cells caused by a reciprocal translocation of the long arms of chromosome 9 and 22. In HLA-A*0201 positive individuals response after interferon-alpha (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 downregulated in remission under imatinib therapy (0 of 7 MBN-positive patients). In contrast, MBN transcription was readily detectable in the peripheral blood in 8 of 8 tested IFN-patients in complete remission (p=0.0002). IFN-dependent MBN transcription was confirmed in vitro by stimulation of peripheral blood mononuclaer cells (PBMC) with IFN and by IFN-mediated activation of the MBN promoter in reporter gene assays. Finally, using HLA-A*0201 restricted, MBN-specific tetrameric complexes, it was demonstrated that all out of four 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 = 0.011). Together, the induction of MBN expression by IFNbut not imatinib may contribute to the specific ability of IFN to induce a 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 that therefore a therapy modality combining IFN and imatinib may be most effective. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Nardi, O. 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