{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:03:20Z","timestamp":1756512200803,"version":"3.44.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"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. Oncol."],"abstract":"<jats:p>Large Granular Lymphocytic Leukemia (LGLL) is a rare clonal proliferative disorder of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, characterized by persistent expansion of large granular lymphocytes (LGLs) in peripheral blood for over six months. According to the 2022 World Health Organization (WHO) classification, LGLL is categorized into T-LGLL, NK-large granular lymphocytic leukemia (NK-LGLL). Aggressive natural killer cell leukemia (ANKL), as a Mature T-cell and NK-cell leukemia independent of LGLL, also has morphologic characteristics of large granular lymphocytes. This report describes a rare case of NK-LGLL transforming into ANKL. This case highlights the necessity of differential diagnosis in LGLL and suggests that proteasome inhibitors combined with immune checkpoint inhibitors may represent a promising therapeutic strategy for ANKL.<\/jats:p>","DOI":"10.3389\/fonc.2025.1648711","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T04:11:14Z","timestamp":1756440674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Transformation of natural killer-cell large granular lymphocytic leukemia to aggressive natural killer cell leukemia"],"prefix":"10.3389","volume":"15","author":[{"given":"Wen","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijie","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.68","article-title":"Population-based analyses among 184 patients diagnosed with large granular lymphocyte leukemia in the Netherlands between 2001 and 2013","volume":"30","author":"Dinmohamed","year":"2016","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41392-025-02164-4","article-title":"Thalidomide-based regimen shows promising efficacy in large granular lymphocytic leukemia: a multicenter phase II study","volume":"10","author":"Yu","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2016.59","article-title":"A population-based study of large granular lymphocyte leukemia","volume":"6","author":"Shah","year":"2016","journal-title":"Blood Cancer J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.018481","article-title":"Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases","volume":"95","author":"Bareau","year":"2010","journal-title":"Haematologica"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2017.1284585","article-title":"Large granular lymphocytic leukemia. 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