Blood Cancer Journal ( IF 12.9 ) Pub Date : 2024-01-18 , DOI: 10.1038/s41408-024-00977-0
Gianpietro Semenzato 1, 2 , Giulia Calabretto 1, 2 , Antonella Teramo 1, 2 , Vanessa Rebecca Gasparini 1, 2 , Elisa Rampazzo 1, 2 , Gregorio Barilà 1, 2, 3 , Renato Zambello 1, 2
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Type T Large Granular Lymphocyte Leukemia (T-LGLL) is a chronic disorder characterized by the abnormal proliferation of clonal cytotoxic T cells. The intriguing association of T-LGLL with autoimmune and inflammatory diseases, the most prominent example being rheumatoid arthritis, raises questions about the underlying pathophysiologic relationships between these disorders which share several biological and clinical features, most notably neutropenia, which is considered as a clinical hallmark. Recent progress in molecular genetics has contributed to a better understanding of pathogenetic mechanisms, thus moving our knowledge in the field of LGL leukemias forward. Focusing on the constitutive activation of STAT3 pathway and the well-established role of STAT3 mutations in T-LGLL, we herein discuss whether the T cell clones occurring in comorbid conditions are the cause or the consequence of the immune-inflammatory associated events. Overall, this review sheds light on the intricate relationships between inflammation and cancer, emphasizing the importance of the STAT3 gene and its activation in the pathophysiology of these conditions. Gaining a deeper understanding of these underlying mechanisms seeks to pave the way for the development of novel targeted therapies for patients affected by inflammation-related cancers.
中文翻译:
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STAT3基因的组成性激活及其突变处于LGL白血病和自身免疫性疾病的十字路口
T 型大颗粒淋巴细胞白血病 (T-LGLL) 是一种慢性疾病,其特征是克隆细胞毒性 T 细胞异常增殖。 T-LGLL 与自身免疫性和炎症性疾病(最突出的例子是类风湿性关节炎)之间有趣的关联,引发了人们对这些疾病之间潜在病理生理学关系的疑问,这些疾病具有多种生物学和临床特征,最显着的是中性粒细胞减少症,这被认为是临床标志。分子遗传学的最新进展有助于更好地了解发病机制,从而推动我们对 LGL 白血病领域的了解。重点关注 STAT3 通路的组成型激活以及STAT3突变在 T-LGLL 中的既定作用,我们在此讨论共病条件下发生的 T 细胞克隆是否是免疫炎症相关事件的原因或结果。总的来说,这篇综述揭示了炎症和癌症之间的复杂关系,强调了 STAT3 基因及其激活在这些疾病的病理生理学中的重要性。更深入地了解这些潜在机制旨在为受炎症相关癌症影响的患者开发新型靶向疗法铺平道路。