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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2002-01-0073.
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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2926-2931
NEOPLASIA
Constitutive expression of SOCS3 confers resistance to IFN- in
chronic myelogenous leukemia cells
Ikuya Sakai,
Kazuto Takeuchi,
Hayato Yamauchi,
Hirosi Narumi, and
Shigeru Fujita
From the First Department of Internal Medicine, Ehime
University School of Medicine, Ehime, Japan.
Because suppressor of cytokine signaling (SOCS) proteins are
negative regulators 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 treatment with interferon (IFN- ). In contrast, the
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 patients in CML blast crisis,
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.

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