Establishment of ganglioside GD2-expressing extranodal NK/T-cell lymphoma cell line with scRNA-seq analysis
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL), known for its poor prognosis and association with Epstein-Barr virus, has a new development with the establishment of the ENKL-J1 cell line. Derived from a patient's bone marrow, ENKL-J1 cells express the ganglioside GD2, making them targets for GD2-directed chimeric antigen receptor T cells. This discovery positions GD2 as a potential therapeutic target. Genetic analysis of ENKL-J1 revealed variants in TP53 and TET2. Single-cell RNA sequencing indicated high expression of genes in key oncogenic pathways such as JAK-STAT, NF-?B, and MAPK, along with genes linked to multidrug resistance, tumor suppression, and anti-apoptosis. In vitro, molecular targeting agents like eprenetapopt, tazemetostat, and vorinostat effectively induced apoptosis in these cells, with GD2-directed T cells also showing cytotoxicity in vivo. The ENKL-J1 cell line, therefore, provides valuable insights for developing treatments for ENKL, especially in advanced stages. Overall design: We performed single-cell RNA sequencing (scRNA-seq) to better capture the characteristics of ENKL-J1.