起源于大颗粒淋巴细胞的T细胞白血病（T-LGL白血病）是一种罕见的淋巴肿瘤，其特征是细胞膜上表达αβ或γδ T细胞受体（TCR）的大颗粒T淋巴细胞克隆性增殖。 γδT-LGL 白血病约占所有 T-LGL 白血病病例的 17%，与自身免疫性疾病相关。然而，风湿病患者中γδT-LGL白血病的特征仍不充分。本项回顾性研究纳入了15例风湿病相关γδT-LGL白血病患者。这些患者来自 2008 年至 2023 年的单一中心。收集了与临床特征和风湿病诊断相关的数据。免疫表型评估以及 T 淋巴细胞克隆性（基于 TCR-γ、TCR-β 和 TCR-δ 基因重排）以及信号转导子和转录激活子 (STAT) 三和 STAT5B 突变分析（通过新一代测序）对血液、骨髓和脾脏样本进行了检查。除一名患者外，所有患者均患有类风湿性关节炎 (RA)。 36%的患者在RA临床表现之前或同时出现γδT-LGL白血病的表现。 60% 的患者出现脾肿大，93% 的患者出现中性粒细胞减少 (<1.5 × 109/L)。各 7 例检测到 CD4-/CD8- 和 CD4-/CD8 亚型。 80% 的患者检测到 STAT3 突变；然而，未检测到 STAT5B 突变。对血液、骨髓和脾组织中 STAT3 的 T 细胞克隆性和变异等位基因频率的评估揭示了 CD4-/CD8-γδT-LGL 白血病的不寻常变异，主要累及脾脏，累及骨髓γδT-LGL白血病可能诱发部分患者发生RA的机制尚需进一步研究。 RA 相关性 γδT-LGL 白血病伴中性粒细胞减少和脾肿大，但外周血中未检测到肿瘤相关淋巴细胞（即所谓的 T-LGL 白血病的脾变异型），诊断困难，可能误诊为 Felty 综合征或肝脾 T -细胞淋巴瘤。版权所有 © 2024 Gorodetskiy、Sidorova、Biderman、Kupryshina、Ryzhikova 和 Sudarikov。

T-cell leukemia originating from large granular lymphocytes (T-LGL leukemia) is a rare lymphoid neoplasia characterized by clonal proliferation of large granular T lymphocytes expressing αβ or γδ T-cell receptor (TCR) on the cell membrane. γδT-LGL leukemia, accounting for approximately 17% of all T-LGL leukemia cases, is associated with autoimmune diseases. However, the features of γδT-LGL leukemia in patients with rheumatologic diseases are still insufficiently characterized.In this retrospective study, 15 patients with rheumatologic disease-associated γδT-LGL leukemia were included. The patients were obtained from a single center from 2008 to 2023. Data related to clinical characteristics and rheumatologic diagnoses were collected. Immunophenotype evaluations as well as T-lymphocyte clonality (based on TCR-γ, TCR-β, and TCR-δ gene rearrangements), and signal transducer and activator of transcription (STAT) three and STAT5B mutation analyses (by next-generation sequencing) were performed on blood, bone marrow, and spleen samples.All but one patient had rheumatoid arthritis (RA). In 36% of patients, manifestations of γδT-LGL leukemia were present before or concurrently with clinical manifestations of RA. Splenomegaly was observed in 60% of patients and neutropenia (<1.5 × 109/L) was detected in 93% of cases. CD4-/CD8- and CD4-/CD8+ subtypes were detected in seven cases each. Mutations in STAT3 were detected in 80% of patients; however, STAT5B mutations were not detected. Evaluations of T-cell clonality and variant allele frequencies at STAT3 in the blood, bone marrow, and spleen tissue revealed an unusual variant of CD4-/CD8- γδT-LGL leukemia with predominant involvement of the spleen, involvement of the bone marrow to a less extent, and no tumor cells in peripheral blood.The mechanism by which γδT-LGL leukemia may induce the development of RA in some patients requires further investigation. Cases of RA-associated γδT-LGL leukemia with neutropenia and splenomegaly but no detectable tumor-associated lymphocytes in peripheral blood (the so-called splenic variant of T-LGL leukemia) are difficult to diagnose and may be misdiagnosed as Felty syndrome or hepatosplenic T-cell lymphoma.Copyright © 2024 Gorodetskiy, Sidorova, Biderman, Kupryshina, Ryzhikova and Sudarikov.