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Initial expression of interferon alpha receptor 2 (IFNAR2) on CD34‐positive cells and its down‐regulation correlate with clinical response to interferon therapy in chronic myelogenous leukemia
Author(s) -
Ito Kinro,
Tanaka Hideo,
Ito Takuo,
Sultana Tanvira A.,
Kyo Taiichi,
Imanaka Fumio,
Ohmoto Yasukazu,
Kimura Akiro
Publication year - 2004
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2004.00275.x
Subject(s) - chronic myelogenous leukemia , interferon , cd34 , alpha interferon , receptor , flow cytometry , immunology , medicine , leukemia , cytokine , cancer research , biology , stem cell , microbiology and biotechnology
In order to investigate the mechanism of interferon‐ α (IFN α ) action in the treatment of chronic myelogenous leukemia (CML), we examined surface expressions of both type I interferon receptor 1 (IFNAR1) and 2 (IFNAR2) subunits on CD34‐positive cells in bone marrow (BM) in a total of 57 CML patients. Initial cell‐surface IFNAR2 expression at diagnosis assessed by flow cytometry widely distributed but showed overall significantly higher expression in CML patients when compared with normal controls. In 15 fresh patients who subsequently received IFN α therapy, IFNAR2 expression at diagnosis was significantly higher in cytogenetic good responders than in poor responders. Down‐regulation of IFNAR2 expression during IFN α therapy was observed only in good responders but not in poor responders. In addition to protein level, both initial high IFNAR2c mRNA expression level and its down‐regulation during IFN α therapy, in purified CD34‐positive cells, were also observed only in good responders. In contrast to IFNAR2, cell‐surface IFNAR1 expression was generally lower than IFNAR2, and correlation between either the pretreatment level or down‐regulation of IFNAR1 and clinical response was not evident. With in vitro IFN α stimulation, CD34‐positive cells showed down‐regulations of cell‐surface IFNAR2, and IFNAR1 to a lesser extent, in one good‐responder patient, but not in one poor‐responder patient. Serum soluble interferon receptor (sIFNR) was higher in untreated CML patients than in normal controls, without any correlation with clinical response to IFN α . Thus, the pretreatment protein and mRNA expression levels of IFNAR2 and their down‐regulations during IFN α therapy correlate well with IFN α response in CML patients.