{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:45:31Z","timestamp":1777045531372,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>T-cell leukemia originating from large granular lymphocytes (T-LGL leukemia) is a rare lymphoid neoplasia characterized by clonal proliferation of large granular T lymphocytes expressing \u03b1\u03b2 or \u03b3\u03b4 T-cell receptor (TCR) on the cell membrane. \u03b3\u03b4T-LGL leukemia, accounting for approximately 17% of all T-LGL leukemia cases, is associated with autoimmune diseases. However, the features of \u03b3\u03b4T-LGL leukemia in patients with rheumatologic diseases are still insufficiently characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective study, 15 patients with rheumatologic disease-associated \u03b3\u03b4T-LGL leukemia were included. The patients were obtained from a single center from 2008 to 2023. Data related to clinical characteristics and rheumatologic diagnoses were collected. Immunophenotype evaluations as well as T-lymphocyte clonality (based on <jats:italic>TCR-\u03b3<\/jats:italic>, <jats:italic>TCR-\u03b2<\/jats:italic>, and <jats:italic>TCR-\u03b4<\/jats:italic> gene rearrangements), and signal transducer and activator of transcription (<jats:italic>STAT<\/jats:italic>) three and <jats:italic>STAT5B<\/jats:italic> mutation analyses (by next-generation sequencing) were performed on blood, bone marrow, and spleen samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All but one patient had rheumatoid arthritis (RA). In 36% of patients, manifestations of \u03b3\u03b4T-LGL leukemia were present before or concurrently with clinical manifestations of RA. Splenomegaly was observed in 60% of patients and neutropenia (&amp;lt;1.5 \u00d7 10<jats:sup>9<\/jats:sup>\/L) was detected in 93% of cases. CD4<jats:sup>\u2212<\/jats:sup>\/CD8<jats:sup>\u2212<\/jats:sup> and CD4<jats:sup>\u2212<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> subtypes were detected in seven cases each. Mutations in <jats:italic>STAT3<\/jats:italic> were detected in 80% of patients; however, <jats:italic>STAT5B<\/jats:italic> mutations were not detected. Evaluations of T-cell clonality and variant allele frequencies at <jats:italic>STAT3<\/jats:italic> in the blood, bone marrow, and spleen tissue revealed an unusual variant of CD4<jats:sup>\u2212<\/jats:sup>\/CD8<jats:sup>\u2212<\/jats:sup> \u03b3\u03b4T-LGL leukemia with predominant involvement of the spleen, involvement of the bone marrow to a less extent, and no tumor cells in peripheral blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The mechanism by which \u03b3\u03b4T-LGL leukemia may induce the development of RA in some patients requires further investigation. Cases of RA-associated \u03b3\u03b4T-LGL leukemia with neutropenia and splenomegaly but no detectable tumor-associated lymphocytes in peripheral blood (the so-called splenic variant of T-LGL leukemia) are difficult to diagnose and may be misdiagnosed as Felty syndrome or hepatosplenic T-cell lymphoma.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2024.1434676","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T06:14:00Z","timestamp":1722838440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gamma-delta T-cell large granular lymphocytic leukemia in the setting of rheumatologic diseases"],"prefix":"10.3389","volume":"12","author":[{"given":"Vadim","family":"Gorodetskiy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Sidorova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bella","family":"Biderman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Kupryshina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya","family":"Ryzhikova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Sudarikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e26742","DOI":"10.7759\/cureus.26742","article-title":"Unusual presentation of T-cell large granular lymphocytic leukemia","volume":"14","author":"Abu Rous","year":"2022","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/cyto.b.20063","article-title":"Flow cytometric immunophenotypic profiles of mature gamma delta T-cell malignancies involving peripheral blood and bone marrow","volume":"67","author":"Ahmad","year":"2005","journal-title":"Cytom. 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