Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression.
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- M Dancescu
- University of Montreal, Notre-Dame Hospital Research Center, Canada.
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- M Rubio-Trujillo
- University of Montreal, Notre-Dame Hospital Research Center, Canada.
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- G Biron
- University of Montreal, Notre-Dame Hospital Research Center, Canada.
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- D Bron
- University of Montreal, Notre-Dame Hospital Research Center, Canada.
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- G Delespesse
- University of Montreal, Notre-Dame Hospital Research Center, Canada.
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- M Sarfati
- University of Montreal, Notre-Dame Hospital Research Center, Canada.
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Abstract
<jats:p>B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells arrested at the intermediate stage of their differentiation. We previously showed that interleukin 4 (IL-4) not only inhibits but also prevents the proliferation of B-CLL cells. We report here that IL-4 protects the B-CLL cells from death by apoptosis (programmed cell death [PCD]). IL-4 inhibits spontaneous and hydrocortisone (HC)-induced PCD of highly purified B cells from 12 unselected CLL patients, as shown by sustained cell viability and lack of DNA fragmentation. IL-1, -2, -3, -5, -6, -7, tumor necrosis factor alpha, and transforming growth factor beta have no protective effect. The in vitro rescue from apoptosis by IL-4 is reflected by an increased expression of Bcl-2 protein, a proto-oncogene directly involved in the prolongation of cell survival in vivo and in vitro. Hence, IL-4-treated B-CLL cells express significantly more Bcl-2 than unstimulated, HC-treated, or fresh B-CLL cells. Furthermore, subcutaneous injection of IL-4 into one CLL patient enhances Bcl-2 protein expression in the leukemic B cells. These data may suggest that IL-4 prevents apoptosis of B-CLL cells using a Bcl-2-dependent pathway. Given our recent observations that fresh T cells from B-CLL patients express IL-4 mRNA, we propose that IL-4 has an essential role in the pathogenesis of CLL disease, by preventing both the death and the proliferation of the malignant B cells.</jats:p>
Journal
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- The Journal of experimental medicine
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The Journal of experimental medicine 176 (5), 1319-1326, 1992-11-01
Rockefeller University Press
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Keywords
Details 詳細情報について
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- CRID
- 1363107369771823744
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- NII Article ID
- 30017432674
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- NII Book ID
- AA00697559
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- ISSN
- 15409538
- 00221007
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- Data Source
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- Crossref
- CiNii Articles