{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:59:01Z","timestamp":1793876341727,"version":"4.7.0"},"reference-count":116,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,31]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative chronic disorder characterized by expansion of either T or natural killer (NK) cytotoxic cells. In contrast to Epstein-Barr virus\u2013induced aggressive NK-LGLL, chronic T-LGLL and NK-LGLL are indolent diseases affecting older patients with a median age of 66.5 years. LGLL is frequently associated with autoimmune disorders, most frequently rheumatoid arthritis. An auto-\/alloantigen is tentatively implicated in disease initiation. Large granular lymphocyte expansion is then triggered by proinflammatory cytokines such as interleukin-15, macrophage inflammatory protein 1 (MIP-1), and RANTES (regulated upon activation, normal T cell expressed, and secreted). This proinflammatory environment contributes to deregulation of proliferative and apoptotic pathways. After the initial description of the JAK-STAT pathway signaling activation in the majority of patients, recurrent STAT3 gain-of-function mutations have been reported. The JAK-STAT pathway plays a key role in LGL pathogenesis by promoting survival, proliferation, and cytotoxicity. Several recent advances have been made toward understanding the molecular landscapes of T- and NK-LGLL, identifying multiple recurrent mutations affecting the epigenome, such as TET2 or KMT2D, and cross talk with the immune microenvironment, such as CCL22. Despite an indolent course, published series suggest that the majority of patients eventually need treatment. However, it is noteworthy that many patients may have a long-term observation period without ever requiring therapy. Treatments rely upon immunosuppressive drugs, namely cyclophosphamide, methotrexate, and cyclosporine. Recent advances have led to the development of targeted approaches, including JAK-STAT inhibitors, cytokine targeting, and hypomethylating agents, opening new developments in a still-incurable disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023021790","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T16:01:43Z","timestamp":1717776103000},"page":"1910-1923","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":34,"title":["A modern view of LGL leukemia"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-2169","authenticated-orcid":false,"given":"Tony","family":"Marchand","sequence":"first","affiliation":[{"name":"1Department of Hematology, Rennes University Hospital, Rennes, France"},{"name":"2Faculty of Medicine, Rennes University, Rennes, France"},{"name":"3UMR 1236, Rennes University, INSERM, \u00c9tablissement Fran\u00e7ais du Sang Bretagne, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lamy","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Rennes University Hospital, Rennes, France"},{"name":"2Faculty of Medicine, Rennes University, Rennes, France"},{"name":"3UMR 1236, Rennes University, INSERM, \u00c9tablissement Fran\u00e7ais du Sang Bretagne, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Thomas P.","family":"Loughran","sequence":"additional","affiliation":[{"name":"4Division of Hematology and Oncology, Department of Medicine and University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"6","key":"2024103115205893800_bib1","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1038\/leu.2016.68","article-title":"Population-based analyses 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