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Some Reflections on P-Glycoprotein Expression in Acute Leukemia

  • Conference paper
Acute Leukemias VII

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 39))

  • 121 Accesses

Abstract

Expression and functional activity of P-gp were measured in 182 acute myelogenous leukemia (AML) patients: 136 patients were treated with the AML-6 protocol (EORTC), containing daunorubicin, vincristine and conventional-dose cytarabine (ara-C), and 21 patients with idarubicin, vepeside and conventional-dose ara-C (ICE-AML-10 protocol/EORTC). Additional 25 patients were treated with a modified dose of idarubicin and ara-C as compared to the ICE protocol, however with the same dose of etopside (ICE-I protocol). P-gp was determined using monoclonal antibody 4E3.16 and functional activity using the rhodamine 123 accumulation test. P-gp positivity was defined as a KS D value ≥ 0.15, P-gp negativity as a KS D value < 0.15. P-gp activity was defined as a ratio of mean rhodamine 123 accumulation with/without verapamil. In AML patients at primary diagnosis and early relapse/refractoriness a significant (p < 0.05) difference between P-gp positive and P-gp negative patients was ascertained using the AML-6 protocol; the difference corresponded to the complete remission rate. For ICE and ICE-I-treated AML patients at primary diagnosis this significance could not be shown. Compared to AML patients at primary diagnosis and patients at early relapse or refractoriness, a significantly (p < 0.05) increased incidence of non-pumping P-gp and a trend (p = 0.054) to a higher percentage of non-P-gp-related mechanisms in AML patients at late relapse was determined. When using the AML-6 protocol, age, activated P-gp and CD34 expression are independent prognostic factors in AML patients. A test system, which determines a functional P-gp overexpression, is a major tool for identifying a poor prognostic group of AML patients. In order to effectively use so-called P-gp modulator substances, the degree of P-gp expression, the activated or non-activated P-gp condition and detection of non-P-gp-related resistance mechanisms are of utmost interest for optimal design and analysis of P-gp modulator trials and for understanding the complexity of chemotherapy-related resistance mechanisms in patients.

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  1. Klinikum Grosshadern, Medizinische Klinik und Poliklinik III, Marchioninistr. 15, D-81377, München, Germany

    V. Nuessler & W. Wilmanns

  2. Institut für Klinische Hämatologie, GSF - Forschungszentrum für Umwelt und Gesundheit GmbH, Marchioninistr. 25, D-81366, München, Germany

    W. Wilmanns

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

    W. Hiddemann  & B. Wörmann  & 

  2. Department of Internal Medicine, USA

    T. Büchner

  3. Department of Pediatrics, University of Münster, Albert-Schweitzer-Straße 33, 48149, Münster, Germany

    J. Ritter  & U. Creutzig  & 

  4. Dept. of Hematology, University of Texas, Anderson Cancer Center, 1515 Holcombe Boulevard, 77030, Houston, Tx., USA

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Nuessler, V., Wilmanns, W. (1998). Some Reflections on P-Glycoprotein Expression in Acute Leukemia. In: Hiddemann, W., et al. Acute Leukemias VII. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71960-8_56

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