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

Abstract

OBJECTIVE:

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.

SUBJECTS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

The KT-1/A3R alpha 1000 subline is a useful model for studying the mechanism of IFN-alpha resistance after IFN-alpha therapy.

• Authors: H Yamauchi, I Sakai, H Narumi, K Takeuchi, S Soga, S Fujita
• Journal: Internal medicine (Tokyo, Japan) (Intern Med) Vol. 40 Issue 7 Pg. 607-12 (Jul 2001) ISSN: 0918-2918 [Print] Japan
• PMID: 11506301 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Interferon-alpha
• Tyrosine

Topics

• Antineoplastic Agents (therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Transformed (drug effects)
• Drug Resistance, Neoplasm (genetics)
• Electrophoresis, Polyacrylamide Gel
• Humans
• Interferon-alpha (therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, metabolism)
• Phosphorylation
• Tyrosine (metabolism)