INHIBITION OF APOPTOTIC CELL-DEATH IN B-CLL BY INTERFERON-GAMMA CORRELATES WITH CLINICAL STAGE

Apoptosis was evaluated in B cells from 41 patients with B-CLL and 20 healthy aged-matched controls. B cells were cultured with and without gamma-IFN and other cytokines; apoptosis was quantified at regular int ervals throughout a 5-day culture period. According to Rai's criteria, 17 patients were classified as good risk, 16 as intermediate and eigh t as high risk. fn vitro, purified B cells from B-CLL patients were ev aluated for apoptosis. Maximal apoptosis (44.12%) was observed at day 5 in cells from patients with poor prognosis. The addition of gamma-IF N to the culture media prevented apoptosis in a dose-dependent manner. Maximal inhibition of apoptosis was achieved with 100 IU/ml of gamma- IFN. The degree of inhibition of apoptosis by gamma-IFN was greater in cells from the high-risk group patients than in those from the interm ediate and good prognosis group (P < 0.0001). The expression of gamma- IFN receptors in B-CLL cells was evaluated using a MnAb against the ex tracellular domain of gamma-IFN receptor. After 4 days in culture with gamma-IFN, only cells from the intermediate- and high-risk groups sho wed an increase in the density of gamma-IFN receptors (P < 0.001). gam ma-IFN was not detected in the sera of our study patients. However gam ma-IFN was detectable in the media from both normal B cells and B-CLL cells in culture; there was no difference in the amount of gamma-IFN r eleased by cells from the three groups of patients studied. Our result s show that in vivo gamma-IFN inhibits apoptosis of B cells from B-CLL patients. The inhibitory effect of gamma-IFN on apoptosis correlates directly with the severity of the disease and this is likely explained by a marked upregulation of gamma-IFN receptors in cells from patient s in the high-risk group.