DataSheet_2_Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing.xlsx

BackgroundT cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, α, β and γ chains were co-existing in a single malignant T cell.Case presentationA 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient’s PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two α chains, one β chain and one γ chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38.ConclusionsWe identified the first TCL case co-expressing α, β and γ chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype.

背景：背景T细胞淋巴瘤（TCL）是一组异质性疾病，包含超过40个亚型。在本研究中，我们鉴定出一种新的TCL亚型，其特征为独特的T细胞受体（TCR）表型，α、β和γ链在同一恶性T细胞中共存。病例报告：一名45岁男性患者在腹部膨胀和肝脏肿大两个月后被诊断为T细胞淋巴瘤。结合组织学审查、PET-CT扫描和免疫表型分析，患者未归类于任何现有的TCL亚型。为更好地理解这一未分类的TCL病例，我们对患者的PBMC和骨髓样本进行了单细胞RNA测序联合TCR测序。令人惊讶的是，我们发现恶性T细胞表达了一种非常罕见的TCR组合，即同时表达两个α链、一个β链和一个γ链。我们进一步研究了这种罕见TCL亚型的分子发病机制和肿瘤细胞异质性。从转录组数据中鉴定出一系列潜在的治疗靶点，例如CCL5、KLRG1和CD38。结论：我们首次发现同时表达α、β和γ链的TCL病例，并对其分子发病机制进行了深入剖析，为该新型TCL亚型的精准医学治疗提供了宝贵的信息。