Expression of Interferon Regulatory Factor 4 in Chronic Myeloid Leukemia: Correlation With Response to Interferon Alfa Therapy

PURPOSE: 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 associa...

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Hauptverfasser: Schmidt, Manuel (VerfasserIn) , Hochhaus, Andreas (VerfasserIn) , König-Merediz, Sven A. (VerfasserIn) , Brendel, Cornelia (VerfasserIn) , Proba, Jutta (VerfasserIn) , Hoppe, Georg J. (VerfasserIn) , Wittig, Burghardt (VerfasserIn) , Ehninger, Gerhard (VerfasserIn) , Hehlmann, Rüdiger (VerfasserIn) , Neubauer, Andreas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2000
In: Journal of clinical oncology
Year: 2000, Jahrgang: 18, Heft: 19, Pages: 3331-3338
ISSN:1527-7755
DOI:10.1200/JCO.2000.18.19.3331
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1200/JCO.2000.18.19.3331
Verlag, lizenzpflichtig, Volltext: https://ascopubs.org/doi/10.1200/JCO.2000.18.19.3331
Volltext
Verfasserangaben:Manuel Schmidt, Andreas Hochhaus, Sven A. König-Merediz, Cornelia Brendel, Jutta Proba, Georg J. Hoppe, Burghardt Wittig, Gerhard Ehninger, Rüdiger Hehlmann, Andreas Neubauer

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520 |a PURPOSE: 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-α) treatment in CML. - - MATERIALS AND 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-α therapy and in 47 additional CML samples taken during IFN-α therapy. IRF4 expression was then correlated with cytogenetic response to IFN-α. - - 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-α 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-α therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-α, a good response was associated with high IRF4 expression. - - CONCLUSION: IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-α therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-α in CML. 
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