{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:05Z","timestamp":1787027765449,"version":"build-2736575974"},"reference-count":137,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disorder characterized by persistent clonal expansion of mature T- or natural killer cells in the blood via chronic antigenic stimulation. LGL leukemia is associated with specific immunophenotypic and molecular features, particularly STAT3 and STAT5 mutations and activation of the JAK-STAT3, Fas\/Fas-L and NF-\u03baB signaling pathways. Disease-related deaths are mainly due to recurrent infections linked to severe neutropenia. The current treatment is based on immunosuppressive therapies, which frequently produce unsatisfactory long-term responses, and for this reason, personalized approaches and targeted therapies are needed. Here, we discuss molecular pathogenesis, clinical presentation, associated autoimmune disorders, and the available treatment options, including emerging therapies.<\/jats:p>","DOI":"10.3390\/cancers16071307","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T12:41:57Z","timestamp":1711543317000},"page":"1307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Large Granular Lymphocytic Leukemia: Clinical Features, Molecular Pathogenesis, Diagnosis and Treatment"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-1202","authenticated-orcid":false,"given":"Fauzia","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-7337","authenticated-orcid":false,"given":"Mariam","family":"Markouli","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Orland","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-6626","authenticated-orcid":false,"given":"Olisaemeka","family":"Ogbue","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-7975","authenticated-orcid":false,"given":"Danai","family":"Dima","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA"},{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44915, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najiullah","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3289-2333","authenticated-orcid":false,"given":"Moaath K.","family":"Mustafa Ali","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA"},{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44915, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood.V82.1.1.bloodjournal8211","article-title":"Clonal diseases of large granular lymphocytes","volume":"82","author":"Loughran","year":"1993","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","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. 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