Development of interferon-α resistant subline from human chronic myelogenous leukemia cell line KT-1

• Published in: Internal medicine (Tokyo, 1992) Vol. 40; no. 7; pp. 607 - 612
• Main Authors: YAMAUCHI, Hayato, SAKAI, Ikuya, NARUMI, Hirosi, TAKEUCHI, Kazuto, SOGA, Shinji, FUJITA, Shigeru
• Format: Journal Article
• Language: English
• Published: Tokyo Japanese Society of Internal Medicine 01.07.2001
• Subjects: Antineoplastic agents; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Transformed - drug effects; Chemotherapy; Drug Resistance, Neoplasm - genetics; Electrophoresis, Polyacrylamide Gel; Humans; Interferon-alpha - therapeutic use; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Medical sciences; Pharmacology. Drug treatments; Phosphorylation; Tyrosine - metabolism; Human; Myeloproliferative syndrome; Chemotherapy; Chronic; Treatment resistance; Alpha interferon; Cytokine; Chronic myelocytic leukemia; Established cell line; Malignant hemopathy; Mechanism
• ISSN: 0918-2918; 1349-7235
• DOI: 10.2169/internalmedicine.40.607

Interferon-alpha (IFN-alpha) 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-alpha therapy. Previously, we established the novel human CML cell line KT-1, which is sensitive to the antiproliferative effects of IFN-alpha. Here, we report the establishment of an IFN-alpha-resistant subline, KT-1/A3R alpha 1000, by culturing KT-1/A3 cells (IFN-alpha-sensitive subline of KT-1) with increasing concentrations of IFN-alpha, in order to analyze the mechanism of acquisition of IFN-alpha resistance in CML cells after IFN-alpha therapy. We developed an IFN-alpha-resistant tumor cell variant, KT-1/A3R alpha 1000, from the KT-1/A3 cell line by culturing cells with increasing concentrations of IFN-alpha. This subline was examined for its ability to proliferate and its resistance to apoptosis in high concentrations of IFN-alpha. The induction of the ISGF3 complex in response to IFN-alpha alpha in KT-1/A3R alpha 1000 was compared with that in the parental cell. The levels of interferon-stimulated gene factor 3 components (STAT1, STAT2, and p48) proteins and STAT2 tyrosine phosphorylation induced after IFN-alpha treatment were unchanged, but formation of the ISGF3 complex was remarkably reduced in KT-1/A3R alpha 1000 cells compared to parental cells. The KT-1/A3R alpha 1000 subline is a useful model for studying the mechanism of IFN-alpha resistance after IFN-alpha therapy.