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 intervals throughout a 5-day culture period. According to Rai's criteria, 17 patients were classified as good risk, 16 as intermediate and eight as high risk. In vitro, purified B cells from B-CLL patients were evaluated for apoptosis. Maximal apoptosis (44.12%) was observed at day 5 in cells from patients with poor prognosis. The addition of gamma-IFN 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 intermediate and good prognosis group (P < 0.0001). The expression of gamma-IFN receptors in B-CLL cells was evaluated using a MnAb against the extracellular domain of gamma-IFN receptor. After 4 days in culture with gamma-IFN, only cells from the intermediate- and high-risk groups showed an increase in the density of gamma-IFN receptors (P < 0.001). gamma-IFN was not detected in the sera of our study patients. However gamma-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 released by cells from the three groups of patients studied. Our results 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 patients in the high-risk group.
Department of Hematology, Reina Sofia Hospital, Cordoba, Spain.
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Rojas
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Roman
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Torres
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Ramirez
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Carracedo
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Lopez
J M
JM
Garcia
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C
Martin
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Pintado
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017471:Receptors, Interferon / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D000970:Antineoplastic Agents; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor