Histone deacetylase inhibitors potently repress CXCR4 chemokine receptor expression and function in acute lymphoblastic leukaemia

Authors

  • Roman Crazzolara,

    1. Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck,
    2. Department of Paediatrics, Innsbruck University Hospital, Innsbruck, Austria,
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  • Karin Jöhrer,

    1. Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck,
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  • Ricky W. Johnstone,

    1. Gene Regulation Laboratory, Peter MacCallum Cancer Institute, Melbourne, Australia,
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  • Richard Greil,

    1. Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck,
    2. Laboratory of Molecular Cytology, Department of Internal Medicine, Innsbruck University Hospital, and
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  • Reinhard K Ofler,

    1. Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck,
    2. Division of Molecular Pathophysiology, Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria
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  • Bernhard Meister,

    1. Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck,
    2. Department of Paediatrics, Innsbruck University Hospital, Innsbruck, Austria,
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  • David Bernhard

    1. Tyrolean Cancer Research Institute (TCRI) at the University of Innsbruck,
    2. Division of Molecular Pathophysiology, Institute of Pathophysiology, University of Innsbruck, Innsbruck, Austria
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Roman Crazzolara, MD, Department of Paediatrics, Innsbruck University Hospital, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail: roman.crazzolara@uibk.ac.at

Abstract

Summary. The chemokine receptor CXCR4 plays a crucial role in the survival and trafficking of leukaemia cells and requires further attention as human immunodeficiency virus type I (HIV-I) utilises CXCR4 as the major coreceptor for cellular entry. We demonstrated that inhibitors of histone deacetylases, currently being tested in clinical trials for the treatment of various tumours, extensively downregulated CXCR4 protein and mRNA levels in leukaemia cell lines and lymphoblasts from patients with childhood acute leukaemia. As a result, the ability of stromal cell-derived factor-1 to induce cellular migration was impaired. Repression of CXCR4 transcription by inhibitors of histone deacetylases might therefore represent a promising novel approach in the treatment of acute leukaemias.

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