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CD56 plays a pivotal role in NK-cell maturation linked to cytotoxicity. However, whether CD56 might be associated with distinctive characteristics in NK-LGLL has not been determined. Hence, this study aims to explore potential associations between CD56 and clinical and biological features in 47 patients with NK-LGLL. Above all, anemia (57.4%) was the most prevalent symptom. Patients treated with immunosuppressive therapy showed a favorable outcome with 87.0% achieving remission. Furthermore, when stratifying patients by CD56 expression on tumor cells, the subset of 28 patients (59.6%) with diminished CD56 expression was frequently relevant to symptomatic disease (92.9% vs 15.8%, P\u2005&amp;lt;\u2005.001), comprising anemia (85.7% vs 15.8%, P\u2005&amp;lt;\u2005.001), neutropenia (67.9% vs 0.0%, P\u2005&amp;lt;\u2005.001), and splenomegaly (42.9% vs 10.5%, P\u2005=\u2005.024). Additionally, this subset demonstrated exclusive STAT3 mutation (61.9% vs 0.0%, P\u2005=\u2005.003), elevated CD161 levels (54.5% vs 0.0%, P\u2005&amp;lt;\u2005.001), and bone marrow fibrosis (92.3% vs 50.0%, P\u2005=\u20050.006). Furthermore, they showed shorter time to first treatment (TTFT) (4-year TTFT: 66.7% vs 100.0%, P\u2005=\u2005.083) and first-line progression-free survival (PFS) (median PFS: 26.3 months vs not reached, P\u2005=\u2005.112). Overall, our data indicate that NK-LGLL patients with diminished CD56 expression represent a more aggressive subset compared to those with normal CD56 levels, underscoring the significance of CD56 as a potential prognostic marker and advancing our understanding of the underlying pathogenesis of NK-LGLL.<\/jats:p>","DOI":"10.1093\/oncolo\/oyae350","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T16:57:47Z","timestamp":1741625867000},"source":"Crossref","is-referenced-by-count":1,"title":["Classification of NK-large granular lymphocytic leukemia by CD56 expression"],"prefix":"10.1093","volume":"30","author":[{"given":"Yuxi","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin, 300020 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