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Single‐Cell Multiomics Reveals TCR Clonotype‐Specific Phenotype and Stemness Heterogeneity of T‐ALL Cells
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Single‐Cell Multiomics Reveals TCR Clonotype‐Specific Phenotype and Stemness Heterogeneity of T‐ALL Cells
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Journal Article
Single‐Cell Multiomics Reveals TCR Clonotype‐Specific Phenotype and Stemness Heterogeneity of T‐ALL Cells
2025
Overview
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. Delineation of rewired regulatory networks and TCR clonotype‐specific heterogeneity in T‐ALL cells by single‐cell multiomics, providing critical insights for potential therapeutic targets, disease stratification method and prognosis predictor for T‐ALL.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ clonotype‐specific T‐ALL characteristics
/ Datasets
/ Female
/ Genes
/ Humans
/ Leukemia
/ Male
/ Original
/ Patients
/ Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
/ Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology
/ Receptors, Antigen, T-Cell - genetics
/ Receptors, Antigen, T-Cell - metabolism
/ Receptors, Antigen, T-Cell, alpha-beta - genetics
/ Receptors, Antigen, T-Cell, alpha-beta - metabolism
/ Single-Cell Analysis - methods
