title: 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.
authors.affiliation: Department of Medicine, University of Illinois at Chicago and West Side Veterans Adminstration Medical Center, IL 60607, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.forename: Leonidas C
authors.initials: LC
authors.lastname: Platanias
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins / Q000502:physiology; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D053613:Janus Kinase 1; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000502:physiology*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D009687:Nuclear Proteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases