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Patients with NK\u2010LGLL typically present with an expansion of mature NK cells displaying large granular lymphocyte morphology, a restricted killer Immunoglobulin\u2010like receptor pattern and genetic lesions, including\n                    <jats:italic>TET2<\/jats:italic>\n                    ,\n                    <jats:italic>CCL22<\/jats:italic>\n                    , and\n                    <jats:italic>STAT3<\/jats:italic>\n                    mutations. NK\u2010LGLL generally follows an indolent clinical course and rarely progresses to a stage requiring treatment. The rarity of the disease has significantly hampered precise diagnosis, a deeper understanding of its pathogenesis, the assessment of appropriate clinical trials, and even its classification. This review aims to present the latest insights into genetic, biological, and clinical features of this disorder. In particular, recent advances in genetics and epigenetics, along with emerging knowledge into the role of microenvironment, have uncovered new vulnerabilities in leukemic cells. These findings may have a meaningful impact on defining genomic\u2010driven disease subsets and hold promise for improving outcomes in large granular lymphocyte leukemia patients through the development of personalized, innovative therapies.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70161","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T19:01:57Z","timestamp":1750878117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["NK\u2010type large granular lymphocyte leukemia comes of age"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-4595","authenticated-orcid":false,"given":"Gianpietro","family":"Semenzato","sequence":"first","affiliation":[{"name":"Department of Medicine, Hematology Unit University of Padova Padova Italy"},{"name":"Veneto Institute of Molecular Medicine Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Teramo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology Unit University of Padova Padova Italy"},{"name":"Veneto Institute of Molecular Medicine Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-6115","authenticated-orcid":false,"given":"Gregorio","family":"Baril\u00e0","sequence":"additional","affiliation":[{"name":"Hematology Unit Ospedale San Bortolo Vicenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8646-2932","authenticated-orcid":false,"given":"Giulia","family":"Calabretto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology Unit University of Padova Padova Italy"},{"name":"Veneto Institute of Molecular Medicine Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rampazzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology Unit University of Padova Padova Italy"},{"name":"Veneto Institute of Molecular Medicine Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Buson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology Unit University of Padova Padova Italy"},{"name":"Veneto Institute of Molecular Medicine Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Zambello","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology Unit University of Padova Padova Italy"},{"name":"Veneto Institute of Molecular Medicine Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101058"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021790"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V68.5.1142.1142"},{"key":"e_1_2_17_5_1","volume-title":"The 2008 Revision of the World Health Organization Classification of Lymphoid Neoplasms","author":"Swerdlow SH","year":"2008"},{"key":"e_1_2_17_6_1","first-page":"665","volume-title":"Haematolymphoid Tumours. 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