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The secreted IL-10 suppresses proliferation of normal immune, CD3\/CD28-stimulated peripheral blood mononuclear cells and enhances viability of the ALK+TCL cells. The Treg phenotype of the affected cells is strictly dependent on NPM\/ALK expression and function as demonstrated by transfection of the kinase into BaF3 cells and inhibition of its enzymatic activity and expression in ALK+TCL cells. NPM\/ALK, in turn, induces the phenotype through activation of its key signal transmitter, signal transducer and activator of transcription 3 (STAT3). These findings identify a mechanism of NPM\/ALK-mediated oncogenesis based on induction of the Treg phenotype of the transformed CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. These results also provide an additional rationale to therapeutically target the chimeric kinase and\/or STAT3 in ALK+TCL.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0603507103","type":"journal-article","created":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T20:48:51Z","timestamp":1149886131000},"page":"9964-9969","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":133,"title":["Nucleophosmin\/anaplastic lymphoma kinase (NPM\/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3"],"prefix":"10.1073","volume":"103","author":[{"given":"Monika","family":"Kasprzycka","sequence":"first","affiliation":[{"name":"*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283; and"},{"name":"Department of Clinical Immunology, Medical University of Warsaw, 02-006 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Marzec","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Liu","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz A.","family":"Wasik","sequence":"additional","affiliation":[{"name":"*Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,6,27]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"S81","volume":"118","author":"Wasik M. 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