17p Deletion is associated with resistance of B-cell chronic lymphocytic leukemia cells to in vitro fludarabine-induced apoptosis

We explored the relationship between the cytogenetic biologic characteristics of B-chronic lymphocytic leukemia (B-CLL) cells and their tendency to undergo spontaneous or fludarabine-induced apoptosis in vitro. B cells from 36 B-CLL patients were incubated with or without fludarabine for 48 h. Apopt...

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Bibliographic Details
Published in:Leukemia & lymphoma 2007-02, Vol.48 (2), p.311-320
Main Authors: Turgut, Burhan, Vural, Ozden, Pala, Funda S., Pamuk, Gülsüm E., Tabakcio lu, Kiymet, Demir, Muzaffer, Öngören, eniz, Soysal, Teoman, Algüne, Çetin
Format: Article
Language:English
Subjects:
17p deletion
ADP-ribosyl Cyclase 1 - metabolism
Aged
Aged, 80 and over
Antineoplastic Agents - pharmacology
apoptosis
Apoptosis - drug effects
Chromosome Deletion
Chromosomes, Human, Pair 17 - genetics
Chronic lymphocytic leukemia
DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors
Female
Flow Cytometry
fludarabine
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Male
Middle Aged
Proto-Oncogene Proteins c-bcl-2 - metabolism
Tumor Suppressor Protein p53 - metabolism
Vidarabine - analogs & derivatives
Vidarabine - pharmacology
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Summary:We explored the relationship between the cytogenetic biologic characteristics of B-chronic lymphocytic leukemia (B-CLL) cells and their tendency to undergo spontaneous or fludarabine-induced apoptosis in vitro. B cells from 36 B-CLL patients were incubated with or without fludarabine for 48 h. Apoptosis was determined by two assays: annexin V staining and DNA staining. Fluorescence in situ hybridization was used for detection of trisomy 12, 11q deletion, and 17p deletion. Bcl-2 and CD38 expressions were determined by flow cytometry. Five patients had 17p deletion, 6 had trisomy 12, and another 6 had 11q deletion. B-CLL cells with 17p deletion had significant resistance to apoptosis induced by fludarabine and a slight spontaneous resistance to apoptosis. Bcl-2 and CD38 were not associated with in vitro spontaneous and fludarabine-induced apoptosis. In conclusion, 17p deletion, which causes loss of p53 gene, is associated with resistance to fludarabine-induced apoptosis in vitro. New treatment modalities should be tried in B-CLL patients with 17p deletion.
ISSN:1042-8194
1029-2403
DOI:10.1080/10428190601059829