{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:24:00Z","timestamp":1789097040782,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"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. Med."],"abstract":"<jats:p>A persistently increased T-cell large granular lymphocyte (T-LGL) count in the blood of more than 2 \u00d7 10<jats:sup>9<\/jats:sup>\/L for at least 6 months is necessary for a reliable diagnosis of T-LGL leukemia. In cases with LGL counts of approximately 0.5\u20132 \u00d7 10<jats:sup>9<\/jats:sup>\/L, a diagnosis of T-LGL leukemia can be made if clonal rearrangement of T-cell receptor (<jats:italic>TCR<\/jats:italic>) genes is present and if the patient shows typical manifestations of T-LGL leukemia, such as cytopenia, splenomegaly, or concomitant autoimmune disease. However, in cases with LGL counts of less than 0.5 \u00d7 10<jats:sup>9<\/jats:sup>\/L, the diagnosis of T-LGL leukemia is questionable (termed as \u201cgray-zone\u201d cases). Although mutations in signal transducer and activator of transcription 3 (<jats:italic>STAT3<\/jats:italic>) gene are the molecular hallmark of T-LGL leukemia, their diagnostic value in the \u201cgray-zone\u201d cases of T-LGL leukemia has not been evaluated \u2013 our study has been aimed to examine the prevalence of <jats:italic>STAT3<\/jats:italic> mutations in these cases. Herein, we describe 25 patients with autoimmune rheumatic diseases, neutropenia, clonal rearrangement of <jats:italic>TCR<\/jats:italic> genes, and circulating LGL count of less than 0.5 \u00d7 10<jats:sup>9<\/jats:sup>\/L. Splenomegaly was observed in 19 (76%) patients. Mutations in the <jats:italic>STAT3<\/jats:italic> were detected in 56% of patients using next-generation sequencing. Importantly, in 3 patients, no involvement of the blood and bone marrow by malignant LGLs was noted, but examination of splenic tissue revealed infiltration by clonal cytotoxic T-lymphocytes within the red pulp, with greater prominence in the cords. We suggest using the term \u201csplenic variant of T-LGL leukemia\u201d for such cases.<\/jats:p>","DOI":"10.3389\/fmed.2022.1000265","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T06:43:11Z","timestamp":1661928191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["STAT3 mutations in \u201cgray-zone\u201d cases of T-cell large granular lymphocytic leukemia associated with autoimmune rheumatic diseases"],"prefix":"10.3389","volume":"9","author":[{"given":"Vadim","family":"Gorodetskiy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Sidorova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Biderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kupryshina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Ryzhikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Sudarikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/s0037-1963(03)00133-1","article-title":"Clinical features of large granular lymphocyte leukemia.","volume":"40","author":"Lamy","year":"2003","journal-title":"Semin Hematol."},{"key":"B2","first-page":"p. 348","article-title":"T-cell large granular lymphocytic leukemia.","author":"Chan","year":"2017","journal-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 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