{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:37:15Z","timestamp":1768315035752,"version":"3.49.0"},"reference-count":29,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A percentage of celiac disease (CD) patients develop refractory type-2 disease (RCD2), a condition associated with increased risk of enteropathy-associated T-cell-lymphoma (EATL) and without therapeutic option. Therefore, we profiled the miRNome in series of peripheral T-cell lymphomas (PTCLs), CD, RCD1 or 2 and in the murine interleukin-15 (IL15)-transgenic (TG) model of RCD. The transcriptome was analyzed in 18 intestinal T-cell lymphomas (ITLs). Bioinformatics pipelines provided significant microRNA (miRNA) lists and predicted targets that were confirmed in a second set of patients.<\/jats:p>\n               <jats:p>Our data show that ITLs have a unique miRNA profile with respect to other PTCLs. The c-MYC regulated miR-17\/92 cluster distinguishes monomorphic epitheliotropic ITL (MEITL) from EATL and prognosticates EATL outcome. These miRNAs are decreased in IL15-TG mice upon Janus kinase (JAK) inhibition. The random forest algorithm identified a signature of 38 classifier miRNAs, among which, the miR-200 and miR-192\/215 families were progressively lost in RCD2 and ITL-CD, whereas miR-17\/92 and C19MC miRNAs were up-regulated. Accordingly, SMAD3, MDM2, c-Myc and activated-STAT3 were increased in RCD2 and EATL tissues while JAK inhibition in IL15-TG mice restored their levels to baseline.<\/jats:p>\n               <jats:p>Our data suggest that miRNAs circuit supports activation of STAT3 and c-Myc oncogenic signaling in RCD2, thus contributing to lymphomagenesis. This novel understanding might pave the way to personalized medicine approaches for RCD and EATL.<\/jats:p>","DOI":"10.1042\/cs20200032","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T10:34:26Z","timestamp":1589798066000},"page":"1151-1166","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Deregulation of miRNAs-cMYC circuits is a key event in refractory celiac disease type-2 lymphomagenesis"],"prefix":"10.1042","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-6216","authenticated-orcid":false,"given":"Valentina","family":"Vaira","sequence":"first","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Gaudioso","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u00a0Antonella","family":"Laginestra","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Terrasi","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Agostinelli","sequence":"additional","affiliation":[{"name":"Hematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvano","family":"Bosari","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-8645","authenticated-orcid":false,"given":"Antonio","family":"Di Sabatino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine San Matteo Hospital, University of Pavia, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Vanoli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine San Matteo Hospital, University of Pavia, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Paulli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine San Matteo Hospital, University of Pavia, Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leda","family":"Roncoroni","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenza","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyanage\u00a0P.","family":"Perera","sequence":"additional","affiliation":[{"name":"Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD 20892, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Fabris","sequence":"additional","affiliation":[{"name":"Division of Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Vecchi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy"},{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Pileri","sequence":"additional","affiliation":[{"name":"Division of Haematopathology, European Institute of Oncology, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Elli","sequence":"additional","affiliation":[{"name":"Center for the Prevention and Diagnosis of Celiac Disease, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,5,22]]},"reference":[{"key":"2021113011122146800_B1","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1136\/gut.2009.195131","article-title":"Classification and management of refractory coeliac disease","volume":"59","author":"Rubio-Tapia","year":"2010","journal-title":"Gut"},{"key":"2021113011122146800_B2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/S0016-5085(98)70530-X","article-title":"Abnormal intestinal intraepithelial lymphocytes in refractory sprue","volume":"114","author":"Cellier","year":"1998","journal-title":"Gastroenterology"},{"key":"2021113011122146800_B3","doi-asserted-by":"publisher","first-page":"225","DOI":"10.2147\/CEG.S87200","article-title":"Improving outcomes of refractory celiac disease - current and emerging treatment strategies","volume":"9","author":"Woodward","year":"2016","journal-title":"Clin. 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