{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:03:28Z","timestamp":1791914608636,"version":"4.3.4"},"reference-count":96,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T00:00:00Z","timestamp":1572652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["HL-125816"],"award-info":[{"award-number":["HL-125816"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Judith and Stewart Colton Center for Autoimmunity","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Feinberg Lymphoma Foundation, Cutaneous Lymphoma Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"The Irma and Hirschl Charitable Trust","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Drs. Martin and Dorothy Spatz Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"HHMI Medical Fellows Program","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"The Novo Nordisk Research Foundation","award":["NNF14OC0012345"],"award-info":[{"award-number":["NNF14OC0012345"]}]},{"DOI":"10.13039\/501100012331","name":"LEO Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"Danish Cancer Society","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fight Cancer Program","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"The Lundbeck Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>T cell lymphomas comprise a distinct class of non-Hodgkin\u2019s lymphomas, which include mature T and natural killer (NK) cell neoplasms. While each malignancy within this group is characterized by unique clinicopathologic features, dysregulation in the Janus tyrosine family of kinases\/Signal transducer and activator of transcription (JAK\/STAT) signaling pathway, specifically aberrant STAT3 activation, is a common feature among these lymphomas. The mechanisms driving dysregulation vary among T cell lymphoma subtypes and include activating mutations in upstream kinases or STAT3 itself, formation of oncogenic kinases which drive STAT3 activation, loss of negative regulators of STAT3, and the induction of a pro-tumorigenic inflammatory microenvironment. Constitutive STAT3 activation has been associated with the expression of targets able to increase pro-survival signals and provide malignant fitness. Patients with dysregulated STAT3 signaling tend to have inferior clinical outcomes, which underscores the importance of STAT3 signaling in malignant progression. Targeting of STAT3 has shown promising results in pre-clinical studies in T cell lymphoma lines, ex-vivo primary malignant patient cells, and in mouse models of disease. However, targeting this pleotropic pathway in patients has proven difficult. Here we review the recent contributions to our understanding of the role of STAT3 in T cell lymphomagenesis, mechanisms driving STAT3 activation in T cell lymphomas, and current efforts at targeting STAT3 signaling in T cell malignancies.<\/jats:p>","DOI":"10.3390\/cancers11111711","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T04:13:08Z","timestamp":1572840788000},"page":"1711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["STAT3 Dysregulation in Mature T and NK Cell Lymphomas"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-5472","authenticated-orcid":false,"given":"Angelina","family":"Seffens","sequence":"first","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, USA"},{"name":"Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-9051","authenticated-orcid":false,"given":"Alberto","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin","family":"Tegla","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7180-6384","authenticated-orcid":false,"given":"Terkild B.","family":"Buus","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, USA"},{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, DK2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Hymes","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-5624","authenticated-orcid":false,"given":"Niels","family":"\u00d8dum","sequence":"additional","affiliation":[{"name":"LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, DK2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa J.","family":"Geskin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-3791","authenticated-orcid":false,"given":"Sergei B.","family":"Koralov","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1200\/JCO.2008.16.4558","article-title":"International peripheral T-cell and natural killer\/T-cell lymphoma study: Pathology findings and clinical outcomes","volume":"26","author":"Vose","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1093\/jnci\/92.15.1240","article-title":"Cancer Surveillance Series: Non-Hodgkin\u2019s Lymphoma Incidence by Histologic Subtype in the United States From 1978 Through 1995","volume":"92","author":"Groves","year":"2000","journal-title":"J. Nat. Cancer Inst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1182\/blood-2017-11-764357","article-title":"Novel insights into the pathogenesis of T-cell lymphomas","volume":"131","author":"Lim","year":"2018","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","article-title":"STATs and gene regulation","volume":"277","author":"Darnell","year":"1997","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/jcp.10364","article-title":"STAT proteins: From normal control of cellular events to tumorigenesis","volume":"197","author":"Migliavacca","year":"2003","journal-title":"J. Cell Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8150","DOI":"10.1073\/pnas.0501643102","article-title":"STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-\u03b13","volume":"102","author":"Liu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1126\/science.8197455","article-title":"Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins","volume":"264","author":"Darnell","year":"1994","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15114","DOI":"10.1074\/jbc.M312530200","article-title":"Real Time Analysis of STAT3 Nucleocytoplasmic Shuttling","volume":"279","author":"Pranada","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1006\/excr.2001.5405","article-title":"Cell Type-Specific and Tyrosine Phosphorylation-Independent Nuclear Presence of STAT1 and STAT3","volume":"272","author":"Meyer","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"34133","DOI":"10.1074\/jbc.M304531200","article-title":"STATs Dimerize in the Absence of Phosphorylation","volume":"278","author":"Braunstein","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/intimm\/dxr078","article-title":"Transcriptional control of T-cell development","volume":"23","author":"Naito","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1038\/onc.2012.347","article-title":"The role of JAK-STAT signaling in haematological malignancies","volume":"32","author":"Vainchenker","year":"2013","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/cr.2008.18","article-title":"STAT3 as a target for inducing apoptosis in solid and hematological tumors","volume":"18","author":"Turkson","year":"2008","journal-title":"Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1146\/annurev-immunol-110416-120628","article-title":"Disorders of the JAK\/STAT Pathway in T Cell Lymphoma Pathogenesis: Implications for Immunotherapy","volume":"35","author":"Waldmann","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cyto.2016.06.017","article-title":"JAK-STAT signaling in cancer: From cytokines to non-coding genome","volume":"87","author":"Pencik","year":"2016","journal-title":"Cytokine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.immuni.2007.11.016","article-title":"T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma","volume":"28","author":"Yang","year":"2008","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9358","DOI":"10.1074\/jbc.C600321200","article-title":"STAT3 regulates cytokine-mediated generation of inflammatory helper T cells","volume":"282","author":"Yang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cyto.2009.07.003","article-title":"STAT3 in CD4+ T helper cell differentiation and inflammatory diseases","volume":"47","author":"Egwuagu","year":"2009","journal-title":"Cytokine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1084\/jem.20141992","article-title":"STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function","volume":"212","author":"Wilson","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.immuni.2011.11.006","article-title":"Keeping STATs on memory CD8+ T cells","volume":"35","author":"Olson","year":"2011","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.immuni.2010.05.003","article-title":"Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis","volume":"32","author":"Durant","year":"2010","journal-title":"Immunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ccell.2015.03.006","article-title":"European T-Cell Lymphoma Study Group, T-Cell Project: Prospective Collection of Data in Patients with Peripheral T-Cell Lymphoma and the AIRC 5xMille Consortium \u201cGenetics-Driven Targeted Management of Lymphoid Malignancies\u201d. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma","volume":"27","author":"Crescenzo","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41408-018-0138-8","article-title":"Prognostic and therapeutic significance of phosphorylated STAT3 and protein tyrosine phosphatase-6 in peripheral-T cell lymphoma","volume":"8","author":"Han","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1126\/science.8122112","article-title":"Fusion of a Kinase Gene, ALK, to a Nucleolar Protein Gene, NMP, in Non-Hodgkin\u2019s Lymphoma","volume":"263","author":"Morris","year":"1994","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"466","DOI":"10.4049\/jimmunol.168.1.466","article-title":"Multilevel Dysregulation of STAT3 Activation in Anaplastic Lymphoma Kinase-Positive T\/Null-Cell Lymphoma","volume":"168","author":"Zhang","year":"2002","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1182\/blood-2007-04-060715","article-title":"Pathobiology of ALK+ anaplastic large-cell lymphoma","volume":"110","author":"Amin","year":"2007","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/ijlh.12817","article-title":"The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms","volume":"40","author":"Matutes","year":"2017","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1182\/blood-2017-12-821868","article-title":"Genetic subtyping of breast implant-associated anaplastic large cell lymphoma","volume":"132","author":"Oishi","year":"2018","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1111\/cas.14114","article-title":"Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T-cell leukemia\/lymphoma","volume":"110","author":"Morichika","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1056\/NEJMoa1114885","article-title":"Somatic STAT3 mutations in large granular lymphocytic leukemia","volume":"366","author":"Koskela","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/leu.2017.49","article-title":"Genomic landscape characterization of large granular lymphocyte leukemia with a systems genetics approach","volume":"31","author":"Coppe","year":"2017","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1182\/blood-2012-06-435297","article-title":"STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte Leukemia","volume":"120","author":"Jerez","year":"2012","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1158\/2159-8290.CD-16-0330","article-title":"The Genetic Basis of Hepatosplenic T-cell Lymphoma","volume":"7","author":"McKinney","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6025","DOI":"10.1038\/ncomms7025","article-title":"Activating mutations of STAT5B and STAT3 in lymphomas derived from \u03b3\u03b4-T or NK cells","volume":"6","author":"Jiang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1038\/leu.2014.200","article-title":"Frequent STAT5B mutations in \u03b3\u03b4 hepatosplenic T-cell lymphomas","volume":"28","author":"Nicolae","year":"2014","journal-title":"Leukemia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/leu.2009.91","article-title":"STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK\/T-cell lymphoma","volume":"23","author":"Coppo","year":"2009","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1084\/jem.20160894","article-title":"Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2","volume":"214","author":"Moffitt","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0140-6736(08)60420-1","article-title":"Mycosis fungoides and S\u00e9zary syndrome","volume":"371","author":"Hwang","year":"2008","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0889-8588(18)30055-8","article-title":"Prognosis and staging of cutaneous T-cell lymphoma","volume":"9","author":"Foss","year":"1995","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1001\/archderm.139.7.857","article-title":"Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: Clinical prognostic factors and risk for disease progression","volume":"139","author":"Kim","year":"2003","journal-title":"Arch. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fujii, K. (2018). New Therapies and Immunological Findings in Cutaneous T-Cell Lymphoma. Front. Oncol.","DOI":"10.3389\/fonc.2018.00198"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6764","DOI":"10.1073\/pnas.94.13.6764","article-title":"Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: Tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines","volume":"94","author":"Nielsen","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/sj.leu.2403385","article-title":"In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3","volume":"18","author":"Sommer","year":"2004","journal-title":"Leukemia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1038\/sj.jid.5701246","article-title":"Cucurbitacin I inhibits Stat3 and induces apoptosis in Sezary cells","volume":"128","author":"Willemze","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/sj.leu.2402093","article-title":"Constitutive STAT3-activation in Sezary syndrome: Tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells","volume":"15","author":"Eriksen","year":"2001","journal-title":"Leukemia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00019","article-title":"Genomic Profiling of T-Cell Neoplasms Reveals Frequent JAK1 and JAK3 Mutations with Clonal Evasion from Targeted Therapies","volume":"2","author":"Greenplate","year":"2018","journal-title":"JCO Precis. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/sj.onc.1205152","article-title":"Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death","volume":"21","author":"Zamo","year":"2002","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1749-6632.2009.04911.x","article-title":"Signal transducer and activator of transcription-3, inflammation, and cancer: How intimate is the relationship?","volume":"1171","author":"Aggarwal","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1182\/blood-2002-05-1343","article-title":"NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors","volume":"101","author":"Chiarle","year":"2003","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nm1249","article-title":"Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target","volume":"11","author":"Chiarle","year":"2005","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/S0002-9440(10)64629-9","article-title":"Lack of Phosphotyrosine Phosphatase SHP-1 Expression in Malignant T-Cell Lymphoma Cells Results from Methylation of the SHP-1 Promoter","volume":"157","author":"Zhang","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1182\/blood-2004-03-1151","article-title":"Methylation of SHP1 gene and loss of SHP1 protein expression are frequent in systemic anaplastic large cell lymphoma","volume":"104","author":"Khoury","year":"2004","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1182\/blood-2006-04-017434","article-title":"Loss of SHP1 enhances JAK3\/STAT3 signaling and decreases proteasome degradation of JAK3 and NPM-ALK in ALK","volume":"108","author":"Han","year":"2006","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1309\/FNY8Y4H6PK1V2MGE","article-title":"Expression of anaplastic lymphoma kinase, tyrosine-phosphorylated STAT3, and associated factors in pediatric anaplastic large cell lymphoma: A report from the children\u2019s oncology group","volume":"127","author":"Nasr","year":"2007","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1182\/blood-2010-09-301994","article-title":"MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression","volume":"117","author":"Desjobert","year":"2011","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1038\/leu.2017.103","article-title":"PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma","volume":"31","author":"Atsaves","year":"2017","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20852","DOI":"10.1073\/pnas.0810958105","article-title":"Oncogenic kinase NPM\/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)","volume":"105","author":"Marzec","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bandini, C., Pupuleku, A., Spaccarotella, E., Pellegrino, E., Wang, R., Vitale, N., Duval, C., Cantarella, D., Rinaldi, A., and Provero, P. (2018). IRF4 Mediates the Oncogenic Effects of STAT3 in Anaplastic Large Cell Lymphomas. Cancers, 10.","DOI":"10.3390\/cancers10010021"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1182\/blood-2014-08-594507","article-title":"Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma","volume":"125","author":"Weilemann","year":"2015","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1073\/pnas.1700682114","article-title":"Cytokine receptor signaling is required for the survival of ALK\u2212 anaplastic large cell lymphoma, even in the presence of JAK1\/STAT3 mutations","volume":"114","author":"Chen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/path.4539","article-title":"Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation","volume":"236","author":"Merkel","year":"2015","journal-title":"J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1182\/blood-2013-10-531509","article-title":"A targeted mutational landscape of angioimmunoblastic T-cell lymphoma","volume":"123","author":"Odejide","year":"2014","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14290","DOI":"10.1038\/ncomms14290","article-title":"THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors","volume":"8","author":"Cayrol","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1182\/blood-2018-99-112123","article-title":"Durable Responses Observed with JAK Inhibition in T-Cell Lymphomas","volume":"132","author":"Moskowitz","year":"2018","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1038\/leu.2015.263","article-title":"Activating somatic mutations outside the SH2-domain of STAT3 in LGL-Leukemia","volume":"30","author":"Andersson","year":"2016","journal-title":"Leukemia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1172\/JCI9940","article-title":"Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression","volume":"107","author":"Liu","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_67","first-page":"3219","article-title":"JAK3\/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK\/T-cell lymphoma, nasal type","volume":"41","author":"Liu","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1182\/blood-2014-07-588970","article-title":"Receptor-type tyrosine-protein phosphatase k directly targets STAT3 activation for tumor suppression in nasal NK\/T-cell lymphoma","volume":"125","author":"Chen","year":"2015","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1182\/blood-2018-01-829424","article-title":"Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer\/T cell lymphoma","volume":"132","author":"Laurensia","year":"2018","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1182\/blood-2016-12-756841","article-title":"PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK\/T-cell lymphoma failing l-asparaginase","volume":"129","author":"Kwong","year":"2017","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"31077","DOI":"10.18632\/oncotarget.25780","article-title":"STAT3 is constitutively activated in chronic active Epstein-Barr virus infection and can be a therapeutic target","volume":"9","author":"Onozawa","year":"2018","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10620","DOI":"10.1073\/pnas.96.19.10620","article-title":"Inhibition of protein phosphatase 2A induces serine\/threonine phosphorylation, subcellular redistribution, and functional inhibition of STAT3","volume":"96","author":"Woetmann","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/jid.2011.293","article-title":"Autocrine IL-21 Stimulation Is Involved in the Maintenance of Constitutive STAT3 Activation in S\u00e9zary Syndrome","volume":"132","author":"Samsom","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"342","DOI":"10.2478\/s11658-010-0008-2","article-title":"STAT3 knockdown by siRNA induces apoptosis in human cutaneous T-cell lymphoma line Hut78 via downregulation of Bcl-xL","volume":"15","author":"Verma","year":"2010","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/jid.2010.349","article-title":"MicroRNA-21 expression in CD4+ T cells is regulated by STAT3 and is pathologically involved in S\u00e9zary syndrome","volume":"131","author":"Qin","year":"2011","journal-title":"J. Invest. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20555","DOI":"10.18632\/oncotarget.4111","article-title":"Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma","volume":"6","author":"Sibbesen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1158\/1078-0432.CCR-15-1784","article-title":"STAT3\/5-dependent IL9 overexpression contributes to neoplastic cell survival in mycosis fungoides","volume":"22","author":"Wei","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.jid.2017.10.028","article-title":"Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma","volume":"138","author":"Fanok","year":"2018","journal-title":"J. Invest. Dermatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1038\/jid.2011.27","article-title":"Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3\/Stat3 signaling pathway","volume":"131","author":"Krejsgaard","year":"2011","journal-title":"J. Invest. Dermatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1182\/blood.V97.4.1056","article-title":"STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma","volume":"97","author":"Brender","year":"2001","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1182\/blood-2015-11-685032","article-title":"Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia","volume":"127","author":"Bellon","year":"2016","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.semcancer.2017.03.006","article-title":"Mechanisms governing metastatic dormancy in breast cancer","volume":"44","author":"Dittmer","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.biopha.2018.02.043","article-title":"MiR-21 attenuates apoptosis-triggered by amyloid-\u03b2 via modulating PDCD4\/PI3K\/AKT\/GSK-3\u03b2 pathway in SH-SY5Y cells","volume":"101","author":"Feng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/bjh.12157","article-title":"MicroRNAs and lymphomagenesis: A functional review","volume":"160","author":"Lawrie","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/sj.leu.2403610","article-title":"Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNalpha","volume":"19","author":"Brender","year":"2005","journal-title":"Leukemia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6645","DOI":"10.1021\/jm300207s","article-title":"Small molecule inhibitors of signal transducer and activator of transcription 3 (Stat3) protein","volume":"55","author":"Debnath","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: New and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1586\/eci.12.19","article-title":"Tofacitinib for the treatment of rheumatoid arthritis","volume":"8","author":"Zerbini","year":"2012","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1182\/blood-2017-10-810739","article-title":"Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1\/2 inhibitor therapy","volume":"132","author":"Porpaczy","year":"2018","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"45443","DOI":"10.1074\/jbc.M107527200","article-title":"Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation","volume":"276","author":"Turkson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1021\/cb700186x","article-title":"Rationally designed inhibitors identify STAT3 N-domain as a promising anticancer drug target","volume":"2","author":"Timofeeva","year":"2007","journal-title":"ACS Chem. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13619-015-0015-x","article-title":"Pharmacological manipulation of transcription factor protein-protein interactions: Opportunities and obstacles","volume":"4","author":"Fontaine","year":"2015","journal-title":"Cell Regen."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00280-014-2480-2","article-title":"Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors","volume":"74","author":"Bendell","year":"2014","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/13543784.2017.1351941","article-title":"Do STAT3 inhibitors have potential in the future for cancer therapy?","volume":"26","author":"Wong","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/annonc\/mdv026","article-title":"Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies","volume":"26","author":"Wong","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/jid.2010.255","article-title":"Stat3 as a therapeutic target for the treatment of psoriasis: A clinical feasibility study with STA-21, a Stat3 inhibitor","volume":"131","author":"Miyoshi","year":"2011","journal-title":"J. Invest. Dermatol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/11\/1711\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:31:29Z","timestamp":1760189489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/11\/1711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,2]]},"references-count":96,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["cancers11111711"],"URL":"https:\/\/doi.org\/10.3390\/cancers11111711","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,2]]}}}