{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:19:46Z","timestamp":1791206386109,"version":"4.1.0"},"reference-count":37,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A characteristic feature of neoplastic transformation is the loss of external control by cytokines and extracellular matrix of cellular differentiation, migration, and mitogenesis. Because suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that an aberrant SOCS expression plays a role in neoplastic transformation. This study reports on a constitutive SOCS-3 expression in cutaneous T-cell lymphoma (CTCL) cell lines. SOCS-3 protein is constitutively expressed in tumor cell lines (but not in nonmalignant T cells) obtained from affected skin from a patient with mycosis fungoides (MF) and from peripheral blood from a patient with Sezary syndrome (SS). In contrast, constitutive SOCS-3 expression is not found in the leukemic Jurkat T-cell line, the MOLT-4 acute lymphoblastic leukemia cell line, and the monocytic leukemic cell line U937. Expression of SOCS-3 coincides with a constitutive activation of STAT3 in CTCL tumor cells, and stable transfection of CTCL tumor cells with a dominant negative STAT3 strongly inhibits SOCS-3 expression, whereas transfection with wild-type STAT3 does not. Moreover, the reduced SOCS-3 expression in cells transfected with the dominant negative STAT3 is associated with an increased sensitivity to interferon-\u03b1 (IFN-\u03b1). In conclusion, evidence is provided for a constitutive SOCS-3 expression in cancer cells obtained from patients with CTCL. Moreover, the findings indicate that the aberrant expression of SOCS-3 is mediated by a constitutive activation of STAT3 in CTCL cells and affects the IFN-\u03b1 sensitivity of these cells.<\/jats:p>","DOI":"10.1182\/blood.v97.4.1056","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"1056-1062","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":105,"title":["STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma"],"prefix":"10.1182","volume":"97","author":[{"given":"Christine","family":"Brender","sequence":"first","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Nielsen","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keld","family":"Kaltoft","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Wasik","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Billestrup","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"\u00d8dum","sequence":"additional","affiliation":[{"name":"From the Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Institute of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA; and Signal Transduction, Novo Nordisk Discovery, Bagsv\u00e6rd, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217584419900_B1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer.","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell."},{"key":"2020021217584419900_B2","doi-asserted-by":"crossref","first-page":"9215","DOI":"10.1073\/pnas.89.19.9215","article-title":"Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression.","volume":"89","author":"Lu","year":"1992","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021217584419900_B3","first-page":"519","article-title":"Expression of multi-cytokine resistance and multi-growth factor independence in advanced stage metastatic cancer. 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