Development of Interferon-α Resistant Subline from Human Chronic Myelogenous Leukemia Cell Line KT-1

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概要

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• Objective Interferon-alpha (IFN-α) is one of the most effective therapeutic agents for a number of hematological malignancies, including chronic myelogenous leukemia (CML). Nevertheless, its efficacy is limited because of the development of resistance to IFN-α therapy. Previously, we established the novel human CML cell line KT-1, which is sensitive to the antiproliferative effects of IFN-α. Here, we report the establishment of an IFN-α-resistant subline, KTl/A3Rα 1000, by culturing KT-1/A3 cells (IFN-α-sensitive subline of KT-1) with increasing concentrations of IFN-α, in order to analyze the mechanism of acquisition of IFN-α resistance in CML cells after IFN-α therapy. Subjects and Methods We developed an IFN-α-resistant tumor cell variant, KT-1/A3Rα 1000, from the KT-1/A3 cell line by culturing cells with increasing concentrations of IFNα. This subline was examined for its ability to proliferate and its resistance to apoptosis in high concentrations of IFNα. The induction of the ISGF3 complex in response to IFNα in KT-1/A3Rα 1000 was compared with that in the parental cell. Results The levels of interferon-stimulated gene factor 3 components (STAT1, STAT2, and p48) proteins and STAT2 tyrosine phosphorylation induced after IFN-α treatment were unchanged, but formation of the ISGF3 complex was remarkably reduced in KT-1/A3Rα 1000 cells compared to parental cells. Conclusion The KT-1/A3Rα 1000 subline is a useful model for studying the mechanism of IFN-α resistance after IFN-a therapy.(Internal Medicine 40: 607-612, 2001)

• 社団法人 日本内科学会の論文

著者

• Fujita Shigeru

  Division Of Blood Transfusion Ehime University School Of Medicine

• YAMAUCHI Hayato

  First Department of Internal Medicine, Ehime University School of Medicine

• Sakai Ikuya

  Department Of Pathophysiology Faculty Of Pharmaceutical Sciences Matsuyama University

• Yamauchi Hayato

  First Department Of Internal Medicine Ehime University School Of Medicine

• Fujita S

  Ehime Univ. School Of Medicine Ehime Jpn

• Fujita Shigeru

  The First Department Of Internal Medicine Ehime University School Of Medicine

• Sakai I

  Ehime Univ. School Of Medicine Ehime Jpn

• YAMAUCHI Hayato

  the First Department of Internal Medicine, Ehime University School of Medicine

• SAKAI Ikuya

  the First Department of Internal Medicine, Ehime University School of Medicine

• NARUMI Hirosi

  the First Department of Internal Medicine, Ehime University School of Medicine

• TAKEUCHI Kazuto

  the First Department of Internal Medicine, Ehime University School of Medicine

• SOGA Shinji

  the First Department of Internal Medicine, Ehime University School of Medicine

• Soga Shinji

  The First Department Of Internal Medicine Ehime University School Of Medicine

• Narumi Hirosi

  The First Department Of Internal Medicine Ehime University School Of Medicine

• Takeuchi Kazuto

  The First Department Of Internal Medicine Ehime University School Of Medicine

• Yamauchi Hayato

  The First Department Of Internal Medicine Ehime University School Of Medicine

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