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Chemosensitivity of B cell chronic lymphocytic leukemia and correlated expression of proteins regulating apoptosis, cell cycle and DNA repair

Leukemia volume 14, pages 40–46 (2000)Cite this article

Abstract

B cell chronic lymphocytic leukemia (B-CLL) cannot be cured with conventional chemotherapy. This clinical enigma appears to be at least partially due to the fact that B-CLL cells are resistant to programmed cell death (apoptosis) and that they are arrested in G0/G1 phase of the cell cycle. The reasons for the dysregulation of these two key cellular events in B-CLL are unclear. The present study aimed at determining correlations between the expression levels of proteins regulating apoptosis, cell cycle and DNA repair in B-CLL cells and normal B cells. In addition, the differential sensitivity of B-CLL cells to drug-induced apoptosis was quantified. We show that in B-CLL cells levels of the death-suppressor Bcl-2 correlated positively with those of the pro-apoptotic protein Bax and of the cyclin-dependent kinase (cdk) inhibitor p27Kip1. In B-CLL cells levels of the anti-apoptotic Bcl-xL showed a positive correlation with levels of the 80 kDa regulatory component (Ku80) of the DNA-dependent protein kinase that is involved in DNA double-stranded break repair. These correlations were not detected in normal B cells. The sensitivity of leukemic cells to FLUD but not to ADM, CPM or to DEX was reduced in pre-treated patients. These data support the hypothesis that in B-CLL cells death-modulators and molecules modulating cell cycle and DNA repair are regulated in a coordinated manner.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG Schr 318/4-1). FS was supported by a research fellowship of the DFG (Schr 318/3-1). We gratefully acknowledge the helpful discussions with M Andreeff MD, PhD (MD Anderson Cancer Center, University of Texas) and with H Renz, MD (Charité, Virchow-University Hospital, Berlin). A Mohnhaupt PhD (Charité, Virchow-University Hospital, Berlin) provided invaluable help performing the statistical analyses.

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  1. A Klein and O Miera: AK and OM contributed equally to this work

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  1. Department of Internal Medicine, Hematology and Oncology, Charité, Campus Virchow-Klinikum, Humboldt University, Berlin, Germany

    A Klein, O Miera, O Bauer, S Golfier & F Schriever

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Klein, A., Miera, O., Bauer, O. et al. Chemosensitivity of B cell chronic lymphocytic leukemia and correlated expression of proteins regulating apoptosis, cell cycle and DNA repair. Leukemia 14, 40–46 (2000). https://doi.org/10.1038/sj.leu.2401636

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