The malignant, CD5+ B lymphocytes of B cell chronic lymphocytic leukemia (B-CLL) die by apoptosis in vitro. This is in contrast to the prolonged life span of the leukemic cells in vivo and likely reflects the lack of essential growth factors in the tissue culture medium. We found that interferon gamma (IFN-gamma) inhibits programmed cell death and promotes survival of B-CLL cells in culture. This effect may also be important in vivo: increased serum levels of IFN-gamma, ranging from 60 to > 2,200 pg/ml, were found in 7 of 10 B-CLL samples tested, whereas the sera of 10 healthy individuals did not contain detectable levels of this cytokine (< 20 pg/ml). High levels of IFN-gamma message were detected in RNA from T cell-depleted B-CLL peripheral blood samples by Northern blot analysis. Synthesis of IFN-gamma by B-CLL lymphocytes was confirmed by in situ hybridization and flow cytometry. The majority of B-CLL cells (74-82%) expressed detectable levels of IFN-gamma mRNA, and CD19+ B-CLL cells were labeled with anti-IFN-gamma monoclonal antibodies. These results show that IFN-gamma inhibits programmed cell death in B-CLL cells and suggest that the malignant cells are able to synthesize this cytokine. By delaying apoptosis, IFN-gamma may extend the life span of the malignant cells and thereby contribute to their clonal accumulation.
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1 January 1993
Article|
January 01 1993
Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia.
M Buschle,
M Buschle
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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D Campana,
D Campana
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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S R Carding,
S R Carding
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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C Richard,
C Richard
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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A V Hoffbrand,
A V Hoffbrand
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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M K Brenner
M K Brenner
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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M Buschle
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
D Campana
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
S R Carding
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
C Richard
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
A V Hoffbrand
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
M K Brenner
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1993) 177 (1): 213–218.
Citation
M Buschle, D Campana, S R Carding, C Richard, A V Hoffbrand, M K Brenner; Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia.. J Exp Med 1 January 1993; 177 (1): 213–218. doi: https://doi.org/10.1084/jem.177.1.213
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