title: Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy.
abstract: OBJECTIVE
  Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-alpha) treatment in CML.
  
  
  METHODS
  Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-alpha therapy and in 47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was then correlated with cytogenetic response to IFN-alpha.
  
  
  RESULTS
  IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-alpha therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-alpha, a good response was associated with high IRF4 expression.
  
  
  CONCLUSIONS
  IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-alpha therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-alpha in CML.
authors.affiliation: Zentrum für Innere Medizin, Abteilung Hämatologie/Onkologie/Immunologie, Klinikum der Philipps-Universität Marburg, Marburg.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: S A
authors.initials: SA
authors.lastname: König-Merediz
authors.forename: C
authors.initials: C
authors.lastname: Brendel
authors.forename: J
authors.initials: J
authors.lastname: Proba
authors.forename: G J
authors.initials: GJ
authors.lastname: Hoppe
authors.forename: B
authors.initials: B
authors.lastname: Wittig
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
mesh_terms: D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D015477:Leukemia, Myelomonocytic, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D014407:Tumor Cells, Cultured; D000099218:Interferon Regulatory Factor-4
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4