Marchand Tony, Pastoret Cédric, Moignet Aline, Roussel Mikael, Lamy Thierry
Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France.
Université de Rennes, Rennes, France.
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):143-149. doi: 10.1182/hematology.2024000539.
Large granular lymphocyte (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or natural killer lymphocytes. Neutropenia-related infections and anemia represent the main manifestations. LGL leukemia is frequently associated with autoimmune disorders such as rheumatoid arthritis, Sjögren's syndrome, autoimmune endocrinopathies, vasculitis, or autoimmune cytopenia. Recent advances in the phenotypic and molecular characterization of LGL clones have underscored the pivotal role of a chronic antigenic stimulation and a dysregulation of the Jak/STAT signaling pathway in the pathophysiology linking leukemic-cell expansion and autoimmunity. In more than half of patients, there is a somatic STAT3 mutation. The disease is characterized by an indolent course, but approximately half of all patients will eventually require therapy. The first-line treatment for LGL leukemia is historically based on immunosuppressive agents (methotrexate, cyclophosphamide, or cyclosporine). However, cytokines blocking molecules or Jak/STAT inhibitors represent a new conceptual therapeutic approach for LGL leukemia. In this review, we present an overview of the spectrum of LGL proliferations, potential links between LGL expansion and autoimmunity, and therapeutic approaches.
大颗粒淋巴细胞（LGL）白血病是一种罕见的淋巴细胞增殖性疾病，其特征为克隆性T淋巴细胞或自然杀伤淋巴细胞增多。中性粒细胞减少相关感染和贫血是主要表现。LGL白血病常与自身免疫性疾病相关，如类风湿关节炎、干燥综合征、自身免疫性内分泌病、血管炎或自身免疫性血细胞减少症。LGL克隆的表型和分子特征方面的最新进展凸显了慢性抗原刺激和Jak/STAT信号通路失调在白血病细胞增殖与自身免疫之间病理生理联系中的关键作用。超过半数的患者存在体细胞STAT3突变。该疾病病程进展缓慢，但所有患者中约有一半最终需要接受治疗。LGL白血病的一线治疗历来基于免疫抑制剂（甲氨蝶呤、环磷酰胺或环孢素）。然而，细胞因子阻断分子或Jak/STAT抑制剂代表了一种针对LGL白血病的全新治疗理念。在本综述中，我们概述了LGL增殖的范围、LGL增殖与自身免疫之间的潜在联系以及治疗方法。
