Constitutive expression of SOCS3 confers resistance to IFN-α in chronic myelogenous leukemia cells

• Published in: Blood 2002-10, Vol.100 (8), p.2926-2931
• Main Authors: Sakai, Ikuya, Takeuchi, Kazuto, Yamauchi, Hayato, Narumi, Hirosi, Fujita, Shigeru
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Base Sequence; Biological and medical sciences; Blast Crisis; Cell Division - drug effects; Chemotherapy; DNA Primers; DNA-Binding Proteins - genetics; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic - drug effects; Hematologic and hematopoietic diseases; Humans; Interferon-alpha - toxicity; Interferon-Stimulated Gene Factor 3; Interferon-Stimulated Gene Factor 3, gamma Subunit; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Pharmacology. Drug treatments; Proteins - genetics; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Transcription Factors - genetics; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-01-0073

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 α (IFN-α). In contrast, the KT-1/A3 cell line, in which constitutive expression of SOCS3 is barely detectable, is sensitive to IFN-α treatment. Forced expression of SOCS3 in the KT-1/A3 cell line confers resistance to IFN-α treatment. Furthermore, most of the blast cells from patients in CML blast crisis, which are usually resistant to IFN-α therapy, showed constitutive expression of SOCS3. These findings indicate that constitutive SOCS3 expression affects the IFN-α sensitivity of CML cell lines and blast cells from patients with CML blast crisis.