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Molecular Mechanisms of Ara-C Signalling: Synergy and Antagonism with Interleukin-3

  • Conference paper
Acute Leukemias V

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 37))

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Abstract

Cytosine arabinosde (Ara-C) is the most widely used and most effective agent in the treatment of acute myelogenous leukemia [1]. Several lines of evidence have suggested that the efficacy of Ara-C may be enhanced by its combination with hematopoietic growth factors such as Interleukin (IL)-3 or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) [2]. IL-3 has been shown by several laboratories to enhance Ara-C incoporation into DNA and Ara-C-mediated tumor cell kill by recruiting resting cells into the cell cycle but also by facilitating intracellular Ara-C metabolism into its active compound, Ara-CTP [3,4]. However, other reports have indicated that IL-3 may also confer resistance of acute myelogenous blasts to subsequent Ara-C [5]. It is thought that Ara-C exerts its cytotoxic effects after incorporation into DNA leading to inhibition of chain elongation [6,7]. In addition, more recent reports have indicated that Ara-C also induces features of apoptotic cell death including DNA fragmentation [8]. Ara-C modulates mRNA expression of several proto-oncogenes, such as c-jun, jun-B or c-myc [3,9,10]. Singaling events initiated by Ara-C, however, are still enigmatic. The present article explores signaling cascades initiated by Ara-C and point to their impact in mediating both synergistic and antagonistic effects of Ara-C and IL-3.

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Authors and Affiliations

  1. Department of Medical Oncology and Applied Molecular Biology, Universitätsklinikum Rudolf Virchow, Freie Universität Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany

    Claus Belka, Claudia Sott, Friedhelm Herrmann & Marion A. Brach

Authors
  1. Claus Belka
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  2. Claudia Sott
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  3. Friedhelm Herrmann
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  4. Marion A. Brach
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Editor information

Editors and Affiliations

  1. Department of Internal Medicine, University of Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany

    W. Hiddemann  & W. Plunkett  & 

  2. Department of Internal Medicine, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    T. Büchner

  3. Department of Pediatric Oncology, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    J. Ritter

  4. Department of Internal Medicine, MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    B. Wörmann M.D., Ph.D.  & M. J. Keating M.D., B.S.  & 

  5. Koordinierungsstelle, Deutsche Krebsgesellschaft e.V., Thea-Bähnisch-Weg 12, 30657, Hannover, Germany

    U. Creutzig

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© 1996 Springer-Verlag Berlin Heidelberg

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Belka, C., Sott, C., Herrmann, F., Brach, M.A. (1996). Molecular Mechanisms of Ara-C Signalling: Synergy and Antagonism with Interleukin-3. In: Hiddemann, W., et al. Acute Leukemias V. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78907-6_22

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  • DOI: https://doi.org/10.1007/978-3-642-78907-6_22

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78909-0

  • Online ISBN: 978-3-642-78907-6

  • eBook Packages: Springer Book Archive

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