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LGLL can be associated with numerous other conditions including infections, other malignancies and autoimmune disease. When symptomatic, the mainstay of treatment is immunosuppression. However, time to response can be slow and response rates and durability of response can be disappointing. With improved understanding of the pathogenesis of the disease, new treatments such as JAK inhibitors are showing promise. Increasingly, T\u2010cell clones that do not fulfill the diagnostic criteria for large granular lymphocytic leukemia are being identified, and these can provide diagnostic complexity, especially if associated with cytopenias. Many of these clones have a similar immunophenotype to LGLL. In these cases, bone marrow investigations can be helpful to differentiate between a \u201clow\u2010count\u201d LGLL and T cell clone of uncertain significance (TCUS). Little is known about the natural history of TCUS at present, and so it is advised to monitor patients in a similar fashion as those with monoclonal B lymphocytosis.<\/jats:p>","DOI":"10.1002\/hon.70076","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T17:57:22Z","timestamp":1750010242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diagnosis and Management of Large Granular Lymphocytic Leukaemia and Its Differentiation From T\u00a0Cell Clones of Uncertain Significance"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2752-5814","authenticated-orcid":false,"given":"Dima","family":"El\u2010Sharkawi","sequence":"first","affiliation":[{"name":"Royal Marsden NHS Foundation Trust  Sutton UK"},{"name":"Institute of Cancer Research  Sutton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-0468","authenticated-orcid":false,"given":"Claire","family":"Dearden","sequence":"additional","affiliation":[{"name":"Royal Marsden NHS Foundation Trust  Sutton UK"},{"name":"Institute of Cancer Research  Sutton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2009.0124"},{"issue":"7","key":"e_1_2_11_3_1","first-page":"1207","article-title":"Serologic and Molecular Evidence for a Possible Pathogenetic Role of Viral Infection in CD3\u2010Negative Natural Killer\u2010Type Lymphoproliferative Disease of Granular Lymphocytes","volume":"9","author":"Zambello R.","year":"1995","journal-title":"Leukemia"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.752486"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402643"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.858426"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1309\/ajcpiil1y5qxtibp"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.12.228"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16336"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.533"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19822"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.27310"},{"issue":"1","key":"e_1_2_11_14_1","first-page":"163","article-title":"Pro\u2010Inflammatory Cells Sustain Leukemic Clonal Expansion in T\u2010Cell Large Granular Lymphocyte Leukemia","volume":"109","author":"Vicenzetto C.","year":"2024","journal-title":"Haematologica"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-692590"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.113142"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1114885"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29175-x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-441378"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-223719"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01480-2"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v92.12.4771.424k32_4771_4777"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v95.10.3219"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02323-6"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.26742"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015851"},{"key":"e_1_2_11_27_1","first-page":"585","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow S. 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