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. Leukemia (2000) 14, 40-46.
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Authors | A Klein, O Miera, O Bauer, S Golfier, F Schriever |
Journal | Leukemia
(Leukemia)
Vol. 14
Issue 1
Pg. 40-6
(Jan 2000)
ISSN: 0887-6924 [Print] England |
PMID | 10637475
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Dexamethasone
- Doxorubicin
- Cyclophosphamide
- Vidarabine
- fludarabine
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(genetics)
- Cell Cycle
(genetics)
- Cyclophosphamide
(pharmacology)
- DNA Repair
(genetics)
- Dexamethasone
(pharmacology)
- Doxorubicin
(pharmacology)
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell
(genetics, pathology)
- Tumor Cells, Cultured
- Vidarabine
(analogs & derivatives, pharmacology)
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