Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Pathology and Laboratory Medicine, Diagnostic Molecular Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood Adv. 2024 Jun 25;8(12):3064-3075. doi: 10.1182/bloodadvances.2023011733.
Although significant progress has been made in understanding the genetic basis of primary hemophagocytic lymphohistiocytosis (HLH), the pathogenesis of secondary HLH, the more prevalent form, remains unclear. Among the various conditions giving rise to secondary HLH, HLH in patients with lymphoma (HLH-L) accounts for a substantial proportion. In this study, we investigated the role of somatic mutations in the pathogenesis of HLH-L in a cohort of patients with T- and/or natural killer-cell lymphoma. We identified a 3-time higher frequency of mutations in FAS pathway in patients with HLH-L. Patients harboring these mutations had a 5-time increased HLH-L risk. These mutations were independently associated with inferior outcome. Hence, our study demonstrates the association between somatic mutations in FAS pathway and HLH-L. Further studies are warranted on the mechanistic role of these mutations in HLH-L.
虽然人们在理解原发性噬血细胞性淋巴组织细胞增多症（HLH）的遗传基础方面取得了重大进展，但继发性 HLH（更常见的形式）的发病机制仍不清楚。在引起继发性 HLH 的各种情况下，淋巴瘤相关 HLH（HLH-L）占很大比例。在这项研究中，我们调查了体细胞突变在 T 细胞和/或自然杀伤细胞淋巴瘤患者 HLH-L 发病机制中的作用。我们发现 HLH-L 患者 Fas 通路突变的频率高出 3 倍。携带这些突变的患者 HLH-L 风险增加了 5 倍。这些突变与预后不良独立相关。因此，我们的研究表明 Fas 通路体细胞突变与 HLH-L 之间存在关联。有必要进一步研究这些突变在 HLH-L 中的作用机制。
