Interferon-alpha up-regulates bcl-2 expression and protects B-CLL cells from apoptosis in-vitro and in-vivo

Jewell, A. P., Worman, C. P., Lydyard, P. M., Yong, K. L., Giles, F. J. and Goldstone, A. H. (1994) Interferon-alpha up-regulates bcl-2 expression and protects B-CLL cells from apoptosis in-vitro and in-vivo. British Journal Of Haematology, 88(2), pp. 268-274. ISSN (print) 0007-1048

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Abstract

The bcl-2 oncoprotein, which is involved in the t(14,18) translocation, protects cells against apoptosis. We examined the effects of interferon-alpha (IFN-alpha) on bcl-2 protein expression and apoptosis in B-chronic lymphocytic leukaemia (B-CLL) cells. None of 12 patients with B-CLL examined expressed the t(14,18) translocation; however, all these, and seven other patients, expressed significant levels of bcl-2 protein. In vitro, IFN-alpha (500 U/ml over 18 h) increased bcl-2 expression on CLL cells (to 200 +/- 23% of control MCF, as determined by indirect immunofluorescence and flow cytometry, n = 10, P < 0.001). All of eight patients who received IFN-alpha (3 megaunits subcutaneously three times a week) demonstrated an increase in bcl-2 expression on circulating malignant cells. CLL cells undergo apoptotic cell death when cultured in vitro (35.6 +/- 10.3% DNA fragmentation after 18 h, n = 10). In the presence of IFN-alpha, however, DNA fragmentation was reduced to 6.6 +/- 5.8% (n = 10, P < 0.001). IFN-alpha also protected CLL cells against apoptosis induced by hydrocortisone and gamma irradiation (reducing DNA fragmentation from 63.9 +/- 12.6% to 10.8 +/- 4.5% and from 80 +/- 2.9% to 5.4 +/- 1.6%, respectively, P < 0.001 for both). The protective effect of IFN-alpha was dose dependent, and maintained for up to 24 h. Our data demonstrate that bcl-2 expression and apoptosis of CLL cells can be influenced by cytokines. In addition, it seems unlikely that the observed clinical responses to IFN-alpha in patients with CLL are due to a direct effect on the malignant cells.

Item Type: Article
Uncontrolled Keywords: cll, bcl-2, apoptosis, ifn-alpha, chronic lymphocytic-leukemia, follicular lymphoma, gene-expression, death, dna, differentiation, induction, survival, level
Research Area: Cancer studies
Biological sciences
Faculty, School or Research Centre: Faculty of Health and Social Care Sciences
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Depositing User: Automatic Import Agent
Date Deposited: 28 Jun 2010 10:32
Last Modified: 13 Jul 2010 07:39
URI: http://eprints.kingston.ac.uk/id/eprint/14463

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