Induction of Apoptosis by Chlorodeoxyadenosine and Dexamethasone in B-Chronic Lymphocytic Leukemia

Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. In the present study we examined the ability of dexamethasone (Dex) and chlorodeoxyadenosine (2-CdA) to induce apoptosis in lymphocytes of patients with B-chronic lymphocytic leukemia...

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Published in:Leukemia & lymphoma 1997-12, Vol.28 (1-2), p.153-157
Main Authors: Shenkerman, Galina, Klaper, Ronen, Ness-abramof, Rosane, Vishlitzky, Victor, Zemer, Ruth, Ellis, Martin, Lishner, Michael, Manor, Yosef, Yuklea, Mona S., Shenkman, Louis, Klein, Ami
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Hormonal - pharmacology
Apoptosis
Apoptosis - drug effects
arachidonic acid
Arachidonic Acid - pharmacology
chlorodeoxyadenosine
CLL
Deoxyadenosines - pharmacology
dexamethasone
Dexamethasone - pharmacology
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Tumor Cells, Cultured
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Summary:Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. In the present study we examined the ability of dexamethasone (Dex) and chlorodeoxyadenosine (2-CdA) to induce apoptosis in lymphocytes of patients with B-chronic lymphocytic leukemia (B-CLL). Lymphocytes of 29 untreated patients and 9 healthy controls were isolated and incubated for 24 hours in the presence or absence of either Dex (2 m¨M) (n = 15) or 2-CdA (3 m¨M) (n = 14). Following incubation the cells were harvested and their DNA extracted and analysed for internucleosomal DNA cleavage by UV illumination after electrophoresis on agarose slab gel containing ethidium bromide. In the Dex group, 10 patients showed dexamethasone independent spontaneous apoptosis appearing 24 hours after the start of incubation. These were the only instances of dexamethasone-enhanced apoptosis. Five patients showed no spontaneous or dexamethasone induced apoptosis. Of the 2-CdA group, 5 showed spontaneous apoptosis enhanced by 2-CdA. No spontaneous apoptosis was observed in the cells from 9 other patients, however, 2-CdA induced apoptosis in 8 cases in this group. This study shows that monitoring of apoptosis in CLL may provide important information regarding susceptibility of the cells to drug induced apoptosis.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428199709058341