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To characterise the multiomics features of T\u2010ALL, we conducted integrative analyses using single\u2010cell RNA, TCR and chromatin accessibility sequencing on pre\u2010 and post\u2010treatment peripheral blood and bone marrow samples of the same patients. We found that there is transcriptional rewiring of gene regulatory networks in T\u2010ALL cells. Some transcription factors, such as <jats:italic>TCF3<\/jats:italic> and <jats:italic>KLF3<\/jats:italic>, showed differences in activity and expression levels between T\u2010ALL and normal T cells and were associated with the prognosis of T\u2010ALL patients. Furthermore, we identified multiple malignant TCR clonotypes among the T\u2010ALL cells, where the clonotypes consisted of distinct combinations of the same TCR \u03b1 and \u03b2 chain per patient. The T\u2010ALL cells displayed clonotype\u2010specific immature thymocyte cellular characteristics and response to chemotherapy. Remarkably, T\u2010ALL cells with an orphan TCR\u03b2 chain displayed the strongest stemness and resistance to chemotherapy. Our study provided transcriptome and epigenome characterisation of T\u2010ALL cells categorised by TCR clonotypes, which may be helpful for the development of novel predictive markers to evaluate treatment effectiveness for T\u2010ALL.<\/jats:p>","DOI":"10.1111\/cpr.13786","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:39:56Z","timestamp":1734309596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Single\u2010Cell Multiomics Reveals <scp>TCR<\/scp> Clonotype\u2010Specific Phenotype and Stemness Heterogeneity of T\u2010<scp>ALL<\/scp> Cells"],"prefix":"10.1111","volume":"58","author":[{"given":"Songnan","family":"Sui","sequence":"first","affiliation":[{"name":"Department of Systems Biomedical Sciences, School of Medicine Jinan University  Guangzhou China"},{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of 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