{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:44:57Z","timestamp":1789011897403,"version":"build-2803163510"},"reference-count":33,"publisher":"American Society of Hematology","issue":"9","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>T\u03b3\u03b4 large granular lymphocyte leukemia (LGLL) is a rare variant of T-cell LGLL (T-LGLL) that has been less investigated as compared with the more frequent T\u03b1\u03b2 LGLL, particularly in terms of frequency of STAT3 and STAT5b mutations. In this study, we characterized the clinical and biological features of 137 patients affected by T\u03b3\u03b4 LGLL; data were retrospectively collected from 1997 to 2020 at 8 referral centers. Neutropenia and anemia were the most relevant clinical features, being present in 54.2% and 49.6% of cases, respectively, including severe neutropenia and anemia in \u223c20% of cases each. Among the various treatments, cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 cases were available for STAT3 and STAT5b mutation analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of T\u03b3\u03b4 cases were also compared with a recently published T\u03b1\u03b2 cohort including 129 cases. Though no differences in STAT3 and STAT5b mutational frequency were found, T\u03b3\u03b4 cases more frequently presented with neutropenia (P\u00a0= .0161), anemia (P\u00a0&amp;lt; .0001), severe anemia (P\u00a0= .0065), and thrombocytopenia (P\u00a0= .0187). Moreover, V\u03b42\u2212 cases displayed higher frequency of symptomatic disease. Overall, T\u03b3\u03b4 cases displayed reduced survival with respect to T\u03b1\u03b2 cases (P\u00a0= .0017). Although there was no difference in STAT3 mutation frequency, our results showed that T\u03b3\u03b4 LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared with T\u03b1\u03b2 LGLL.<\/jats:p>","DOI":"10.1182\/blood.2021013489","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T19:27:31Z","timestamp":1663010851000},"page":"1036-1046","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["T\u03b3\u03b4 LGLL identifies a subset with more symptomatic disease: analysis of an international cohort of 137\u00a0patients"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-6115","authenticated-orcid":false,"given":"Gregorio","family":"Baril\u00e0","sequence":"first","affiliation":[{"name":"1Department of Medicine, Hematology and Clinical Immunology Section, Padua University School of Medicine, Padua, Italy"},{"name":"2Veneto Institute of Molecular Medicine, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-8384","authenticated-orcid":false,"given":"Angela","family":"Grassi","sequence":"additional","affiliation":[{"name":"3Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0149-9651","authenticated-orcid":false,"given":"HeeJin","family":"Cheon","sequence":"additional","affiliation":[{"name":"4Department of Medicine and University of Virginia Cancer Center, Division of Hematology & Oncology, University of Virginia School of Medicine, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2754-699X","authenticated-orcid":false,"given":"Antonella","family":"Teramo","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Hematology and Clinical Immunology Section, Padua University School of Medicine, Padua, Italy"},{"name":"2Veneto Institute of Molecular Medicine, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Calabretto","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Hematology and Clinical Immunology Section, Padua University School of Medicine, Padua, Italy"},{"name":"2Veneto Institute of Molecular Medicine, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0397-6418","authenticated-orcid":false,"given":"Jasmanet","family":"Chahal","sequence":"additional","affiliation":[{"name":"4Department of Medicine and University of Virginia Cancer Center, Division of Hematology & Oncology, University of Virginia School of Medicine, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2548-4596","authenticated-orcid":false,"given":"Cristina","family":"Vicenzetto","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Hematology and Clinical Immunology Section, Padua University School of Medicine, Padua, Italy"},{"name":"2Veneto Institute of Molecular Medicine, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-8917","authenticated-orcid":false,"given":"Julia","family":"Almeida","sequence":"additional","affiliation":[{"name":"5Department of Medicine and Cytometry Service, Cancer Research Center (Institute of Molecular and Cell Biology of Cancer\u2013Consejo Superior de Investigaciones Cient\u00edficas\/Universidad de Salamanca), University of Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca and Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryna C.","family":"Shemo","sequence":"additional","affiliation":[{"name":"4Department of Medicine and University of Virginia Cancer Center, Division of Hematology & Oncology, University of Virginia School of Medicine, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"6Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Rebecca","family":"Gasparini","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Hematology and Clinical Immunology Section, Padua University School of Medicine, Padua, Italy"},{"name":"2Veneto Institute of Molecular Medicine, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8381-301X","authenticated-orcid":false,"given":"Noemi","family":"Munoz-Garcia","sequence":"additional","affiliation":[{"name":"5Department of Medicine and Cytometry Service, Cancer Research Center (Institute of Molecular and Cell Biology of Cancer\u2013Consejo Superior de Investigaciones Cient\u00edficas\/Universidad de Salamanca), University of Salamanca, Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca and Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Pastoret","sequence":"additional","affiliation":[{"name":"7Department of Hematology, Rennes University Hospital, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6457-5052","authenticated-orcid":false,"given":"Hideyuki","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"8Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Oshimi","sequence":"additional","affiliation":[{"name":"9Department of Medicine, Division of Hematology, Kushiro Rosai Hospital, Kushiro, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubomir","family":"Sokol","sequence":"additional","affiliation":[{"name":"10Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiro","family":"Ishida","sequence":"additional","affiliation":[{"name":"8Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, 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