{
  "abstract": "Background: Relapse remains the principal cause of treatment failure in pediatric acute leukemia. Clinically validated minimal residual disease (MRD) assays - multiparameter flow cytometry, immunoglobulin/T-cell-receptor rearrangement sequencing, and targeted next-generation sequencing panels -- are highly sensitive but read out predefined features and do not reconstruct clonal architecture or link a cell's genotype to its functional state. We systematically reviewed what single-cell sequencing has revealed about clonal evolution, chemoresistance, the immune microenvironment, and post-therapeutic immune dynamics in this disease. Methods: This review followed PRISMA 2020. PubMed/MEDLINE, the Cochrane Library, and Google Scholar were searched to September 2026 for primary studies applying single-cell DNA, RNA, chromatin-accessibility, surface-protein, or immune-repertoire sequencing to pediatric acute leukemia samples or pediatric-derived models. Risk of bias in non-randomized studies was assessed with ROBINS-I. Because designs, platforms, and outcomes were heterogeneous, findings were synthesized narratively by biologic theme without meta-analysis, following the SWiM guideline. Results: Of 63 records identified, 10 studies were included (published 2016-2026; 6-159 patients or samples per study; up to ~700,000 cells profiled). Single-cell DNA sequencing traced minor NOTCH1-mutant diagnostic subclones into PTEN- or TP53-mutant relapse clones that bulk sequencing missed. Rare dormant, label-retaining cells and developmental-state-dependent drug sensitivity defined chemoresistant compartments. Remodeling of the bone marrow immune microenvironment identified patients with adverse outcome among those classified as MRD-low, and pre-infusion CAR T-cell type 2 functionality and post-transplant cytotoxic memory CD8+ T-cell subsets were associated with durable remission. Of the seven studies assessed with ROBINS-I, four were at moderate and three at serious overall risk of bias, driven chiefly by small, selected cohorts. Conclusions: Single-cell sequencing yields mechanistic insight that complements, rather than replaces, clinically validated MRD assays, and nominates candidate biomarkers for risk stratification, treatment selection, cell-therapy manufacturing, and post-transplant monitoring. The evidence remains preliminary; adequately powered, prospective, and harmonized studies are required before clinical adoption.",
  "abstract_shown": true,
  "affiliations": [
    "Convitto Nazionale Vittorio Emanuele II"
  ],
  "article_type": "Confirmatory results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. Martelli"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Martelli"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5zzhvbqf4j26p.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.757108",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757108v1.full",
  "id": "5zzhvbqf4j26p",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757108v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2739|Acute Lymphoblastic Leukemia research"
    ]
  ],
  "openalex": "W7220866634",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757108v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5zzhvbqf4j26p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:25Z",
      "native_id": "10.64898/2026.10.06.757108",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757108v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Single-Cell Sequencing in Pediatric Acute Leukemia: A Systematic Review of Biologic Insights and Translational Potential",
  "title_text": "Single-Cell Sequencing in Pediatric Acute Leukemia: A Systematic Review of Biologic Insights and Translational Potential",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:25Z",
  "url": "https://research.draconitic.com/paper/5zzhvbqf4j26p",
  "venue": "bioRxiv",
  "versions": []
}