Apoptosis induction by hypercross-linking of the surface antigen CD5 with anti-CD5 monoclonal antibodies in B cell chronic lymphocytic leukemia.
We evaluated cells from 24 patients with B cell chronic lymphocytic leukemia (B-CLL) to determine apoptosis induced by CD5 hypercross-linking. Following the CD5 hypercross-linking with anti-CD5 monoclonal antibodies (MoAbs), we identified 10 patients where CD5 hypercross-linking induced apoptosis (group A) and 14 patients whose cells were resistant to the anti-CD5 MoAbs (group B). The programmed cell death pathway of the cells from patient group A was caspase-3 and poly (ADP-ribose) polymerase (PARP)-dependent, involved a reduction of the mitochondrial transmembrane potential DeltaPsi and a down-regulation of the anti-apoptotic Bcl-2, Mcl-1 and iNOS proteins. Early activation-associated molecules such as CD25 and CD69 were expressed at higher levels than in controls after 6 h of culture with anti-CD5 MoAb. The expression of CD5 and of CD72, the ligand for CD5, were significantly lower in group A compared with group B. Anti-CD20 MoAb had similar activity with anti-CD5 MoAb and the combination of the two MoAbs seemed to be additive. In this study, it is suggested that the cells from some B-CLL patients can be induced into programmed cell death by CD5 hypercross-linking with anti-CD5 MoAbs.
Cioca
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Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Kitano
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology*; D018956:CD5 Antigens / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000502:physiology; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; C494811:BCL2L1 protein, human; D018956:CD5 Antigens; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein