title: Investigating hairy cell leukemia dysregulations. Looking for interferon alpha site of action in hairy cells.
abstract: One of the most striking characteristics of hairy cell leukemia (HCL) is its remarkable responsiveness to alpha-interferon (IFN-alpha) therapy. IFN-alpha is a multifunctional cytokine able to regulate the growth, differentiation and recirculation of normal and malignant B lymphocytes. These activities have been extensively studied in hairy cells, but none of these properties has been shown to fully account for IFN-alpha responsiveness. Numerous data now support the idea that IFN-alpha exerts its therapeutic effect both indirectly, through stimulation of immunocompetent cells, and directly on the hairy cells. Our approach to investigate the mode action of IFN-alpha in HCL has been to identify abnormalities which occur in these tumor cells and then to ascertain whether these abnormalities can be rectified by IFN-alpha treatment. A high level of free Ca2+ in the cytoplasm of hairy cells was identified. Increases in cytosolic Ca2+ are believed to be a pivotal signal in regulating cell proliferation, cell differentiation and cell death. These high Ca2+ levels in hairy cells could be reduced upon treatment with IFN-alpha either in vitro or in vivo, probably acting by reducing Ca2+ influx into the leukemic cells. Moreover, the effect of IFN-alpha on [Ca2+]i seems to be correlated with alteration in the pattern of kinase/phosphatase activities and with down-regulation of CD20 phosphorylation, a B cell specific phosphoprotein involved in Ca2+ influx across the plasma membrane.
authors: Unite 365 INSERM, Institut Curie, Paris, France.
authors: E
authors: E
authors: Genot
authors: J
authors: J
authors: Wietzerbin
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D001665:Binding Sites; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007943:Leukemia, Hairy Cell / Q000503:physiopathology* / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016898:Interferon-alpha