{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T17:20:50Z","timestamp":1779384050484,"version":"3.53.1"},"reference-count":48,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Aim<\/jats:title>\n<jats:p>This study was to explore role of immune landscape and the immune cells in acute lymphoblastic leukemia (ALL) progression.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>The most prevalent genetic alteration in childhood ALL is the ETV6-RUNX1 fusion. The increased proliferation of B progenitor cells could expedite the disease\u2019s progression due to irregularities in the cell cycle. Nevertheless, the mechanisms by which particular cell clusters influence the cell cycle and promote the advancement of ALL are still not well understood.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>This study was to explore role of immune landscape and the immune cells in ALL progression.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Single-cell RNA sequencing (scRNA-seq) data of ETV6-RUNX1 and healthy pediatric samples obtained from <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE132509\">GSE132509<\/jats:uri> were clustered and annotated using the Seurat package, and differentially highly expressed genes identified in each cluster were analyzed using DAVID for pathway annotation. Chromosome amplification and deletion were analyzed using the inferCNV package. SCENIC evaluated the regulation of transcription factors and target gene formation in cells. cellphoneDB and CellChat were served to infer ligand-receptor pairs that mediate interactions between subpopulations. The role of the target gene in regulating ALL progression was assessed using RT-qPCR, Transwell and scratch healing assays.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The bone marrow mononuclear cells (BMMCs) from ETV6-RUNX1 and healthy pediatric samples in <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE132509\">GSE132509<\/jats:uri> were divided into 11 clusters, and B cell cluster 1 was identified as B progenitor cell, which was amplified on chromosome 6p. B progenitor cells were divided into seven clusters. Expression levels of amplified genes in chromosome 6p of B progenitor cell cluster 5 were the highest, and its specific highly expressed genes were annotated to pathways promoting cell cycle progression. Regulons formed in B progenitor cell cluster 5 were all involved in promoting cell cycle progression, so it was regarded as the B progenitor cell cluster that drives cell cycle progression. The key regulator of the B progenitor cell is E2F1, which promotes the migration and invasion ability of the cell line HAP1. The major ligand-receptor pairs that mediate the communication of B progenitor cell cluster 5 with cytotoxic NK\/T cells or naive T cells included FAM3C\u2212CLEC2D, CD47\u2212SIRPG, HLAE\u2212KLRC2, and CD47\u2212KLRC2. HLAE\u2212KLRC1 and TGFB1\u2212(TGFBR1+TGFBR2).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study outlined the immune cell landscape of ETV6-RUNX1 ALL and identified chromosome 6p amplification in B progenitor cells, described the major B progenitor cell cluster driving cell cycle progression and its potential regulatory mechanisms on NK cells and T cells, providing cellular and molecular insights into ETV6-RUNX1 ALL.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.18445","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T09:26:07Z","timestamp":1730453167000},"page":"e18445","source":"Crossref","is-referenced-by-count":2,"title":["Potential molecular mechanisms of ETV6-RUNX1-positive B progenitor cell cluster in acute lymphoblastic leukemia revealed by single-cell RNA sequencing"],"prefix":"10.7717","volume":"12","author":[{"given":"Ning","family":"Qu","sequence":"first","affiliation":[{"name":"Pediatrics 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