Single-cell analysis of immune-lineage features in T-cell large granular lymphocytic leukemia
10.3760/cma.j.cn121090-20241125-00479
- VernacularTitle:单细胞水平解析T细胞大颗粒淋巴细胞白血病免疫谱系特征
- Author:
Ke HUANG
1
;
Lele ZHANG
;
Chen QIU
;
Ruonan LI
;
Yucan SHEN
;
Weiwang LI
;
Hong PAN
;
Zhen GAO
;
Liwei FANG
;
Yajing CHU
;
Weiping YUAN
;
Jun SHI
Author Information
1. 中国医学科学院血液病医院（中国医学科学院血液学研究所），血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020
- Publication Type:Journal Article
- Keywords:
Leukemia, large granular lymphocytic;
Immune cell;
Differentially expressed genes;
Pathway enrichment analysis
- From:
Chinese Journal of Hematology
2025;46(5):453-459
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.
