Effect of interleukin-2 on CD95 (Fas/APO-1) expression in fresh chronic lymphocytic leukaemia and mantle cell lymphoma cells: relationship to ex vivo chemoresponse.
Cells from B-cell chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL) rarely express the CD95 (Fas/APO-1) antigen. Our aims were to determine whether CD95 levels (assessed by flow cytometry) in fresh neoplastic CD19+/CD5+ B-lymphocytes from CLL and MCL could be upregulated using clinically relevant doses of interleukin-2 (IL-2), and to compare this with their ex vivo cytotoxic drug sensitivity (assessed by DiSC assay). CD95-expression was absent/negligible in 13/14 CLL and 7/7 MCL specimens. Following culture (without IL-2) CD95 was expressed on dying CD5+ B-lymphocytes but only on live cells in 2/15 cases. In live cells from 2 CLL specimens, IL-2 caused up-regulation of CD95 and was associated with ex vivo drug resistance. Clinically relevant doses of IL-2 had pleiotropic effects on CD95-levels in fresh CLL cells, but did not induce CD95 in MCL cells. The link between CD95-induction and ex vivo drug resistance may point to a clinically resistant subset of CLL patients.
Bosanquet
A G
AG
Bath Cancer Research, Wolfson Center, Royal United Hospital, U.K. a.g.bosanquet@bath.ac.uk
Bell
P B
PB
Rooney
N
N
D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000494:pharmacology*
D018956:CD5 Antigens; D007376:Interleukin-2; D019014:fas Receptor