Single‐Cell Multiomics Reveals TCR Clonotype‐Specific Phenotype and Stemness Heterogeneity of T‐ ALL Cells

作者：Songnan Sui, Xiaolei Wei, Yue Zhu, Qiuyue Feng, Xianfeng Zha, Lipeng Mao, Boya Huang, Wen Lei, Guobing Chen, Huien Zhan, Huan Chen, Ru Feng, Chengwu Zeng, Yangqiu Li, Oscar Junhong Luo · 发表于：Cell Proliferation · 年份：2024 · DOI：10.1111/cpr.13786 · 被引用次数：4 · 研究领域：Single-cell and spatial transcriptomics、Acute Lymphoblastic Leukemia research、Immune Cell Function and Interaction

T-cell acute lymphoblastic leukaemia (T-ALL) is a heterogeneous malignant disease with high relapse and mortality rates. To characterise the multiomics features of T-ALL, we conducted integrative analyses using single-cell RNA, TCR and chromatin accessibility sequencing on pre- and post-treatment peripheral blood and bone marrow samples of the same patients. We found that there is transcriptional rewiring of gene regulatory networks in T-ALL cells. Some transcription factors, such as TCF3 and KLF3, showed differences in activity and expression levels between T-ALL and normal T cells and were associated with the prognosis of T-ALL patients. Furthermore, we identified multiple malignant TCR clonotypes among the T-ALL cells, where the clonotypes consisted of distinct combinations of the same TCR α and β chain per patient. The T-ALL cells displayed clonotype-specific immature thymocyte cellular characteristics and response to chemotherapy. Remarkably, T-ALL cells with an orphan TCRβ chain displayed the strongest stemness and resistance to chemotherapy. Our study provided transcriptome and epigenome characterisation of T-ALL cells categorised by TCR clonotypes, which may be helpful for the development of novel predictive markers to evaluate treatment effectiveness for T-ALL.