Alpha-interferon (alpha-IFN) protects B-chronic lymphocytic leukaemia cells from apoptotic cell death in vitro.
B-chronic lymphocytic leukaemia cells (CLL) are prone to apoptotic cell death when cultured in vitro. Apoptosis and loss of the bcl-2 protein is prevented in CLL cells cultured in the presence of interleukin-4. In this study we analysed the effects of alpha-IFN on the DNA fragmentation, bcl-2 protein levels and cell survival in purified B-cells from 16 CLL patients. Alpha-IFN (10(3) U/ml) reduced the degree of spontaneous DNA fragmentation of CLL cells after a 30 h culture period (from a mean of 22.2% in control cultures to 10.5%, P < 0.01). This inhibition was accompanied by preservation of bcl-2 protein and an increased survival of CLL cells compared to control cultures. In parallel, alpha-IFN inhibited hydrocortisone induced DNA fragmentation in CLL cells. The effects of alpha-IFN on DNA synthesis of CLL cells were variable (in two patients a decrease and in seven an increase in 3H-thymidine uptake) and did not correlate with the effect on DNA fragmentation. In conclusion, our data suggest that alpha-IFN, like IL-4 and gamma-IFN, inhibits apoptosis of CLL cells. These in vitro data indicate that the clinical responses of some CLL patients to alpha-IFN cannot be explained by a direct cytotoxic effect of alpha-IFN on circulating CLL cells. Alternatively, alpha-IFN may inhibit the proliferation of the small fraction of clonogenic CLL progenitors, or interfere with cellular interactions necessary for the survival and growth of CLL cells.
Panayiotidis
P
P
Department of Haematology, Royal Free Hospital and School of Medicine, London.
Ganeshaguru
K
K
Jabbar
S A
SA
Hoffbrand
A V
AV
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004273:DNA, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000097:blood; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007370:Interferon Type I; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D013936:Thymidine; D006854:Hydrocortisone