title: The interferon-alpha revival in CML.
abstract: Interferon-alpha (IFNα) was once the standard of frontline treatment for chronic myeloid leukemia (CML). Its pleiotropic mechanism of action in CML includes immune activation and specific targeting of CML stem cells. Early studies of IFNα in CML demonstrated that patients in chronic phase could attain extremely stable remissions, which correlated with long-term survival. Some patients even sustained their remission after discontinuing therapy, but the mechanism underlying this phenomenon is not well understood. Today, BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, induce remarkable responses in CML patients and have become the mainstay of CML therapy. Although TKIs target the pathogenic BCR-ABL protein in CML, they cannot fully eradicate CML stem cells. Some of the clinical trials testing IFNα plus imatinib combination therapy suggest that addition of IFNα increases the speed and rate of responses with imatinib therapy. However, the undesirable side effects of IFNα can make this therapy difficult to deliver, and the optimal therapeutic window for using IFNα in combination therapy is unknown. Further studies are needed to clarify the best niche for IFNα use in CML.
authors: Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Comprehensive Cancer Center Room 4302, Ann Arbor, MI, 48109-5936, USA, mtalpaz@umich.edu.
authors: Moshe
authors: M
authors: Talpaz
authors: Jessica
authors: J
authors: Mercer
authors: Rüdiger
authors: R
authors: Hehlmann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D015415:Biomarkers; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016044:Fusion Proteins, bcr-abl; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a