{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:28:59Z","timestamp":1791862139030,"version":"4.3.4"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute lymphoblastic leukemia (ALL) is the most prevalent malignant tumor in children, with B-cell ALL (B-ALL) accounting for 85% of cases. Despite advancements in chemotherapy and supportive care, a subset of high-risk B-ALL patients still experience relapse post-treatment. The molecular mechanisms underlying the relapses after intensified chemotherapy remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrated single-cell multi-omics analysis combining single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) from pediatric high-risk B-ALL patients following early intensified chemotherapy, as well as from healthy controls. Bioinformatic pipelines were applied to assess cellular composition, chromatin accessibility, gene ontology enrichment, spectral clustering, and copy number variation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant differences in cellular composition were observed between the remission and non-remission groups, with the non-remission group exhibiting a notable increase in HSC\/MPP and Pro-B cells. Copy number variation (CNV) analysis also revealed that the CNV levels in HSC\/MPP and Pro-B cells were higher in the non-remission group compared to other cell types. We subsequently identified a subcluster associated with resistance to intensified therapy within both the HSC\/MPP and Pro-B cell groups. The drug-resistant subcluster of HSC\/MPP cells was characterized by high expression of TCF4, EBF1, ERG, AL589693.1, and CRIM1, as well as enrichment of the allograft rejection pathway and the Notch signaling pathway. The drug-resistant subcluster of Pro-B cells was characterized by high expression of RPS29, B2M, RPL41, RPS21, NEIL1, AC007384.1, and CRIM1, as well as enrichment of the B cell receptor signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our study identified distinct cellular subpopulations associated with treatment failure, provide insights into the molecular mechanisms underlying treatment resistance in B-ALL and may inform the development of targeted therapies for high-risk patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1645546","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T09:51:25Z","timestamp":1762941085000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell multi-omics analysis reveals cellular subpopulations associated with relapse in high-risk B-ALL following intensified chemotherapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Li","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children Hematological Oncology and Birth Defects Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kunming Children\u2019s Hospital","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kunming Children\u2019s Hospital","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kunming Children\u2019s Hospital","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Xinqi City People\u2019s Hospital","place":["Xinqi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanjing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sichuan Provincial Woman\u2019s and Children\u2019s Hospital\/The Affiliated Women\u2019s and Children\u2019s Hospital of Chengdu Medical College","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sichuan Provincial Woman\u2019s and Children\u2019s Hospital\/The Affiliated Women\u2019s and Children\u2019s Hospital of Chengdu Medical College","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigang","family":"Yin","sequence":"additional","affiliation":[{"name":"Luzhou Key Laboratory of Nervous System Disease and Brain Function, Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Institute of Brain Science, Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangfan","family":"Xie","sequence":"additional","affiliation":[{"name":"Luzhou Key Laboratory of Nervous System Disease and Brain Function, Southwest Medical University","place":["Luzhou, Sichuan, 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