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Lymphoma

Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma

Leukemia volume 18, pages 1872–1878 (2004)Cite this article

Abstract

Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK+ ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75%) ALK+ tumors were SOCS3 positive and eight (67%) coexpressed pSTAT3. In comparison, 18 of 25 (72%) ALK-- tumors were SOCS3 positive and seven (28%) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK+ tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation.

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Authors and Affiliations

  1. Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    J H Cho-Vega, K Spurgers, Y K Remache & F Gilles

  2. Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    G Z Rassidakis, H M Amin, P Tsioli, F Vega & L Jeffrey Medeiros

  3. Department of Lymphoma-Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    A H Goy

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Correspondence to L Jeffrey Medeiros.

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Cho-Vega, J., Rassidakis, G., Amin, H. et al. Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma. Leukemia 18, 1872–1878 (2004). https://doi.org/10.1038/sj.leu.2403495

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