Interferon-alpha, Bcl-2 expression and apoptosis in B-cell chronic lymphocytic leukemia.
Interferon-alpha has been used as therapy in patients with B-cell chronic lymphocytic leukaemia (B-CLL), and is able to induce remissions in patients with early stage disease. Although interferon-alpha exhibits a wide variety of cellular effects, none of these have adequately explained the mechanism of action of interferon-alpha in B-CLL. Recent attention has focussed on the role of bcl-2 in B-CLL, and the regulation of bcl-2 expression by cytokines. B-CLL is characterized by the relentless accumulation in the peripheral blood and bone marrow of a monoclonal population of long-lived B-cells. However, when these cells are cultured in vitro, they die rapidly by apoptosis or programmed cell death. It has recently been demonstrated that B-CLL cells can be protected from apoptotic death in vitro by co-culture with cytokines, such as IL-1, IL-2, IL-4, IL-6 and interferon-gamma. The protection against apoptosis is correlated with increased levels of bcl-2 expression. It was suggested that interferon-alpha induced remissions in early stage B-CLL by interrupting these growth-factor dependent survival pathways and allowing the cells to die by apoptotic death in vivo. However, interferon-alpha has also been shown to protect B-CLL cells from apoptotic death in vitro. This suggests that interferon-alpha does not produce remission in B-CLL by direct effects on B-CLL cells in the circulation. Many of the cytokines which protect B-CLL cells from apoptotic cell death, are members of the cytokine receptor family which utilize a common family of signal transduction molecules. Further elucidation of these signal transduction pathways may offer the prospect of developing novel therapeutic strategies aimed at inducing apoptosis of the malignant clone in vivo.
School of Life Science, Kingston University, Surrey, UK.
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Jewell
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2