Signaling via the interferon-alpha receptor in chronic myelogenous leukemia cells

Abstract

It is well established that IFNalpha has significant clinical activity in the treatment of chronic myelogenous leukemia (CML). This cytokine has been used for many years in the management of patients in the chronic phase of the disease, but the mechanisms by which it induces growth inhibitory effects in CML-cells have not been elucidated. Understanding the signaling mechanisms by which the Type I IFN receptor transduces growth inhibitory signals in BCR-ABL expressing cells should prove very valuable, as it may result in the design of new, more specific pharmacological compounds that target the same cellular cascades. Recent evidence indicates that, in addition to the classic IFN-activated Jak-Stat pathway, the Type I IFN receptor engages in its signaling cascade the CrkL-adapter protein, which is also a substrate for the kinase activity of the BCR-ABL oncogene. In addition, it appears that activation of a member of the Map kinase (MAPK) family of proteins, the p38 MAPK, is essential for the generation of the antileukemic effects of IFNalpha. This review summarizes the recent advances in the-field of interferon signaling in CML cells and discusses the implications of identifying signaling proteins that mediate IFNalpha-induced growth inhibition.