Upstream mediators of the Fas apoptotic transduction pathway are defective in B-chronic lymphocytic leukemia.
Data concerning the presence and the functionality of Fas receptor in malignant B-cells are controversial. We have analyzed Fas molecules on B-cells from patients with B-chronic lymphocytic leukemia (B-CLL) cells. We observed a large variability, both of percentage of Fas-positive cells and of intensity of Fas level. Fas triggering was inefficient in inducing apoptosis whatever the number of Fas-positive B-cells, the amount of Fas receptors. B-cells were also resistant to etoposide treatment, but able to undergo apoptosis after dexamethasone treatment. We suggest that the Fas apoptotic pathway is altered in B-CLL patients at the initial step(s) of apoptotic machinery.
Roué
G
G
UPRES-EA 2128, UFR de Médecine, Université de Caen, CHU Côte de Nacre, 14032 Cedex, Caen, France.
Lancry
L
L
Duquesne
F
F
Salaün
V
V
Troussard
X
X
Sola
B
B
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D020169:Caspases / Q000378:metabolism / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D005047:Etoposide; D003907:Dexamethasone; D020169:Caspases