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Pharmacologic Modulation of Multidrug Resistance in Acute Leukemia: Results and Challenges

  • 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

The limited curative potential of conventional chemotherapy in patients with acute myeloid leukemia (AML) has directed attention to identification of cellular mechanisms contributing to treatment failure. Intrinsic and/or acquired resistance to antineoplastic remains a clinical challenge for patients with poor-risk AML and relapsed patients. Multidrug resistance (MDR) due to overexpression of the mdr1 gene or its membrane product P-glycoprotein (P-gp), has been implicated as an important cellular mechanism of resistance that contributes to treatment failure in this disease [1]. Indeed, prospective studies in de novo AML have shown that overexpression of mdr1 is associated with a lower complete remission rate and shorter remission duration in patients receiving conventional induction and post-remission therapy [2, 3]. P-gp expression has been linked to a number of adverse prognostic variables including age, secondary leukemia, cytogenetic pattern, and a CD34 surface phenotype [3–6]. Evidence to date, indicates that mdr1 expression is determined in part by the lineage and stage of cellular differentiation that mimics its physiologic regulation in blood cell development. Normal hematopoietic stem cells natively express high levels of mdr1, but a corresponding decrease in gene message is seen with myeloid maturation [7, 8]. These observations suggest that expression of the MDR phenotype in AML, therefore, represents a conserved physiologic function.

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Author information

Authors and Affiliations

  1. Section of Hematology/Oncology and Bone Marrow Transplant Program, Arizona Cancer Center, Tucson, AZ, USA

    Alan F. List, Betty Glinsmann-Gibson & William S. Dalton

  2. Departments of Medicine and Pharmacology/Toxicology, University of Arizona College of Medicine, Tucson, AZ, USA

    Alan F. List, Betty Glinsmann-Gibson & William S. Dalton

Authors
  1. Alan F. List
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  2. Betty Glinsmann-Gibson
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  3. William S. Dalton
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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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List, A.F., Glinsmann-Gibson, B., Dalton, W.S. (1996). Pharmacologic Modulation of Multidrug Resistance in Acute Leukemia: Results and Challenges. 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_11

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  • DOI: https://doi.org/10.1007/978-3-642-78907-6_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78909-0

  • Online ISBN: 978-3-642-78907-6

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