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Involvement of BCL-2 and Bax in the IL-7-lnduced Inhibition of Spontaneous Apoptosis in Childhood T-ALL

  • Conference paper
Acute Leukemias VIII

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 40))

  • 106 Accesses

Abstract

Induction of apoptosis by cytokine deprivation and its inhibition by cytokines in growth factor-dependent cell lines has been demonstrated to be under the control of Bcl-2-related proteins. Recently, we have demonstrated that leukemic cells of patients with newly diagnosed T-ALL underwent spontaneous apoptosis upon culturing in vitroand that this kind of apoptosis could be effectively inhibited by IL-7. In the present study, we addressed the role of Bcl-2 and Bax proteins, the two major members of the Bcl-2 family, in the regulation of spontaneous and IL-7-modulated apoptosis in T-ALL. To this end, we investigated leukemic blasts from childhood T-ALL patients as to expression levels of Bcl-2 and Bax, which were quantified by flow cytometry in units of molecules of equivalent soluble fluorochrome (MESF) before and after the treatment with IL-7 (100 U/ml, 24h, 37°C), and their relative changes were correlated with the extent of apoptosis in leukemic cells in vitro.We found that expression changes of Bax, but not Bcl-2, positively correlated with the extent of spontaneous apoptosis (Spearman correlation: p=0.022 and p=0.991, respectively; 20 patients). By contrast, changes of Bax expression levels did not correlate with the inhibition of apoptosis by IL-7 (p=0.47, 30 patients). However, inhibition of spontaneous apoptosis by IL-7 was associated with upregulation of Bcl-2 and, even stronger, with Bcl-2/Bax ratios (linear regression: r=0.51, p=0.004 and r=0.59, p=0.0006, respectively, 30 patients). Therefore, our data suggest a differential involvement of Bcl-2 and Bax in the induction of spontaneous apoptosis and its regulation by IL-7 in T-ALL.

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Authors and Affiliations

  1. Dept. of Hematology, Oncology and Tumor Immunology, Robert-Rössle-Clinic, Charité, Humboldt-University of Berlin, D-13125, Berlin, Germany

    V. Ruppert, C. Wuchter, B. Dörken, W.-D. Ludwig & L. Karawajew

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  1. V. Ruppert
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  2. C. Wuchter
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  3. B. Dörken
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  4. W.-D. Ludwig
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  5. L. Karawajew
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Editor information

Editors and Affiliations

  1. Department of Internal Medicine A, Germany

    T. Büchner

  2. Department of Internal Medicine III, University Hospital Großhadern Ludwig-Maximilians-University, Marchioninistr. 15, 81377, München, Germany

    W. Hiddemann

  3. Dept. of Internal Medicine, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    B. Wörmann

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

    G. Schellong , J. Ritter  & U. Creutzig ,  & 

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© 2001 Springer-Verlag Berlin Heidelberg

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Ruppert, V., Wuchter, C., Dörken, B., Ludwig, WD., Karawajew, L. (2001). Involvement of BCL-2 and Bax in the IL-7-lnduced Inhibition of Spontaneous Apoptosis in Childhood T-ALL. In: Büchner, T., Hiddemann, W., Wörmann, B., Schellong, G., Ritter, J., Creutzig, U. (eds) Acute Leukemias VIII. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18156-6_23

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  • DOI: https://doi.org/10.1007/978-3-642-18156-6_23

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62109-3

  • Online ISBN: 978-3-642-18156-6

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