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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3714-3722. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-05-089151. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-05-089151v1 111/7/3714    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chatterjee, M. Articles by Bargou, R. C. Search for Related Content PubMed PubMed Citation Articles by Chatterjee, M. Articles by Bargou, R. C. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma Manik Chatterjee1, Christoph Rancso2, Thorsten Stühmer1, Niels Eckstein3, Mindaugas Andrulis4, Christian Gerecke5, Heike Lorentz1, Hans-Dieter Royer3, and Ralf C. Bargou1 1 Department of Internal Medicine II, Division of Hematology, University Hospital of Würzburg, Würzburg; 2 Helios Clinics, Department of Pathology, Berlin; 3 Center for Advanced European Studies and Research (CAESAR), Bonn; 4 Institut of Pathology, University of Heidelberg, Heidelberg; and 5 Department of Hematology, Oncology and Tumorimmunology, Robert Rössle Cancer Center at the Max Delbrück Center for Molecular Medicine, Berlin, Germany Current knowledge about molecular mechanisms underlying disease progression and drug resistance in multiple myeloma (MM) is still limited. Here, we analyzed the potential pathogenetic role of the Y-box binding protein YB-1 in MM. YB-1 is a member of the cold-shock domain protein superfamily and involved in various cellular functions such as proliferation. Immunohistochemical analyses revealed that neither normal bone marrow (BM) plasma cells (PCs), premalignant PCs of patients with monoclonal gammopathy of unknown significance (MGUS), nor MM cells with a mature morphology showed expression of YB-1 in situ. In contrast, YB-1 was strongly expressed in situ in normal PC precursor blasts as well as in a MM subset and in vitro in all of the evaluated MM cell lines. The YB-1–expressing MM cells were characterized by an immature morphology and a highly proliferative phenotype as defined by Ki 67 expression. We observed that siRNA-mediated knockdown of YB-1 decreased proliferation and induced apoptosis in MM cells even in the presence of BM stromal cells. Furthermore, we found that overexpression of YB-1 mediated resistance toward doxorubicin-induced apoptosis in MM cells. Thus, YB-1 contributes to disease progression, survival, and drug resistance in MM and might therefore provide an attractive therapeutic target. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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