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 (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 microM) (n = 15) or 2-CdA (3 microM) (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 apopto sis. 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.
Shenkerman
G
G
Department of Medicine C, Sapir Medical Center, Kfar Saba, Israel.
Klaper
R
R
Ness-Abramof
R
R
Vishlitzky
V
V
Zemer
R
R
Ellis
M
M
Lishner
M
M
Manor
Y
Y
Yuklea
M S
MS
Shenkman
L
L
Klein
A
A
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D003839:Deoxyadenosines; D016718:Arachidonic Acid; D003907:Dexamethasone