Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL), is characterized by Epstein-Barr virus infection and poor prognosis. We established a novel cell line, ENKL-J1, from bone marrow cells of an ENKL patient. We found that ENKL-J1 cells express the ganglioside GD2 (GD2) and that GD2-directed chimeric antigen receptor T cells exhibit cytotoxicity against ENKL-J1 cells, indicating that GD2 would be a suitable target of GD2-expressing ENKL cells. Targeted next-generation sequencing revealed and variants in ENKL-J1 cells. Furthermore, single-cell RNA sequencing in ENKL-J1 cells showed high gene-expression levels in the oncogenic signaling pathways JAK-STAT, NF-κB, and MAPK. Genes related to multidrug resistance (), tumor suppression (), anti-apoptosis (), immune checkpoints (CD274, CD47), and epigenetic regulation () also were expressed at high levels. The molecular targeting agents eprenetapopt, tazemetostat, and vorinostat efficiently induced apoptosis in ENKL-J1 cells . Furthermore, GD2-directed chimeric antigen receptor T cells showed cytotoxicity against ENKL-J1 cells . These findings not only contribute to understanding the molecular and genomic characteristics of ENKL; they also suggest new treatment options for patients with advanced or relapsed ENKL.

中文翻译：

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通过 scRNA-seq 分析建立表达神经节苷脂 GD2 的结外 NK/T 细胞淋巴瘤细胞系

结外自然杀伤 (NK)/鼻型 T 细胞淋巴瘤 (ENKL) 的特点是 Epstein-Barr 病毒感染，预后不良。我们从 ENKL 患者的骨髓细胞中建立了一种新的细胞系 ENKL-J1。我们发现ENKL-J1细胞表达神经节苷脂GD2（GD2），并且GD2定向的嵌合抗原受体T细胞对ENKL-J1细胞表现出细胞毒性，表明GD2将是表达GD2的ENKL细胞的合适靶标。靶向下一代测序揭示了 ENKL-J1 细胞中的变异。此外，ENKL-J1 细胞中的单细胞 RNA 测序显示致癌信号通路 JAK-STAT、NF-κB 和 MAPK 的基因表达水平较高。与多药耐药（）、肿瘤抑制（）、抗凋亡（）、免疫检查点（CD274、CD47）和表观遗传调控（）相关的基因也高水平表达。分子靶向剂 eprenetapopt、tazemetostat 和 vorinostat 有效诱导 ENKL-J1 细胞凋亡。此外，GD2定向嵌合抗原受体T细胞对ENKL-J1细胞表现出细胞毒性。这些发现不仅有助于理解 ENKL 的分子和基因组特征；他们还为晚期或复发性 ENKL 患者提出了新的治疗方案。