Premium
Alpha‐interferon (α‐IFN) protects B‐chronic lymphocytic leukaemia cells from apoptotic cell death in vitro
Author(s) -
Panayiotidis Panayiotis,
Ganeshaguru Kanagasabai,
Aafa Shireen,
Jabbar B.,
Hoffbrand A. Victor
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb03269.x
Subject(s) - dna fragmentation , apoptosis , clonogenic assay , biology , chronic lymphocytic leukemia , cytotoxic t cell , microbiology and biotechnology , programmed cell death , fragmentation (computing) , in vitro , cancer research , immunology , leukemia , biochemistry , ecology
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 α‐IFN on the DNA fragmentation, bcl‐2 protein levels and cell survival in purified B‐cells from 16 CLL patients. α‐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, α‐IFN inhibited hydrocortisone induced DNA fragmentation in CLL cells. The effects of α‐IFN on DNA synthesis of CLL cells were variable (in two patients a decrease and in seven an increase in 3 H‐thymidine uptake) and did not correlate with the effect on DNA fragmentation. In conclusion, our data suggest that α‐IFN, like IL‐4 and γ‐IFN, inhibits apoptosis of CLL cells. These in vitro data indicate that the clinical responses of some CLL patients to α‐IFN cannot be explained by a direct cytotoxic effect of α‐IFN on circulating CLL cells. Alternatively, α‐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.