Interferon alpha and intracytoplasmic free calcium in hairy cell leukemia cells

Hairy cell leukemia (HCL) is a B-cell tumor affecting the pre-plasma stage of B cell differentiation. One of the most striking characteristics of this disease is its remarkable responsiveness to alpha-interferon (IFN-alpha) therapy. Interferons constitute a heterologous family of multifunctional cytokines displaying anti-viral, anti-proliferative and immunoregulatory properties. These activities have been extensively studied in hairy cells, but the mechanism of action of IFN-alpha in hairy cell leukemia remains unknown. 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 down-regulation of CD20 phosphorylation, a B cell specific phosphoprotein involved in Ca2+ influx across the plasma membrane. The possible origins and implications of Ca2+ deregulation and the possible mechanisms or sites of action of IFN-alpha in tumor cells from HCL are explored in this review.