Submitted January 10, 2002
Accepted April 16, 2002
Constitutive expression of SOCS-3 confers resistance to IFN-
in chronic myelogenous leukemia cells
Ikuya Sakai*, Kazuto Takeuchi, Hayato Yamauchi, Hirosi Narumi, and Shigeru Fujita
First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
* Corresponding author; email: ikusakai{at}m.ehime-u.ac.jp.
Because suppressor of cytokine signaling (SOCS) proteins are negative regulator of cytokine-induced signaling, it has been hypothesized that aberrant SOCS expression confers resistance against cytokine therapy. This study reports on the constitutive expression of SOCS3 in most chronic myelogenous leukemia (CML) cell lines, which are resistant to IFN- treatment. In contrast, KT-1/A3 cell line, in which constitutive expression of SOCS3 is barely detectable, is sensitive to IFN- treatment. Forced expression of SOCS3 in the KT-1/A3 cell line confers resistance to IFN- treatment. Furthermore, most of the blast cells from CML blast crisis patients, which are usually resistant to IFN- therapy, showed constitutive expression of SOCS3. These findings indicate that constitutive SOCS3 expression affects the IFN- sensitivity of CML cell lines and blast cells from patients with CML blast crisis.
