{
  "abstract": "Background: Induction failure (IF) after standard induction chemotherapy is associated with poor outcomes in pediatric acute myeloid leukemia (pAML); however, whether established molecular markers such as FLT3-ITD retain prognostic significance across induction response states remains incompletely understood. We characterized the genomic landscape of IF and evaluated the prognostic significance of FLT3-ITD according to induction response. Methods: This multi-cohort study integrated a TARGET discovery cohort (n = 1979) and an independent cohort from the Children’s Hospital of Chongqing Medical University (CHCMU; n = 98). Clinical characteristics, somatic mutations, fusion profiles, and gene–gene interaction patterns were compared between patients with and without IF. Multivariable logistic regression identified genomic factors associated with IF, and survival analyses evaluated the prognostic impact of FLT3-ITD according to induction response. Results: IF was associated with inferior OS (overall survival) (pooled HR = 3.24, 95% CI: 2.66–3.95). FLT3 mutations were consistently enriched in IF patients, whereas KIT mutations and favorable core-binding factor fusions were more frequent among non-IF patients. NUP98-NSD1 fusion was strongly enriched in IF patients in the TARGET cohort. Gene interaction analyses revealed reduced recurrent co-mutation patterns among IF patients. FLT3 mutation independently and reproducibly associated with IF. Among patients achieving induction remission, FLT3-ITD remained associated with inferior OS (HR = 1.34, 95% CI: 1.06–1.69, p = 0.014), whereas no statistically significant additional prognostic effect was detected among patients with IF. Conclusions: This study characterizes the genomic landscape of IF in pAML and identifies FLT3 mutation as a reproducible marker of induction resistance. Achieving induction remission does not eliminate the adverse prognostic significance of FLT3-ITD, supporting the integration of molecular risk and treatment response in subsequent risk stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hematology and Oncology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents’ Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Intelligent Application of Big Data in Pediatrics Engineering Research Center of Chongqing Education Commission of China, Chongqing 400014, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rongqiu Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinghui Cui"
    },
    {
      "affs": [
        0
      ],
      "name": "Lan Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xianmin Guan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yali Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Dou"
    },
    {
      "affs": [
        0
      ],
      "name": "Xianhao Wen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxia Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyan Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyuan Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xing Zeng"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Yu",
      "orcid": "0000-0002-1103-2679"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ee2mj5j6bh0q2.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18203280",
  "fulltext_url": null,
  "id": "ee2mj5j6bh0q2",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/20/3280",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7221549621",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/ee2mj5j6bh0q2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18203280",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/20/3280"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "Genomic Determinants of Induction Failure and Persistent Prognostic Risk of FLT3-ITD in Pediatric Acute Myeloid Leukemia",
  "title_text": "Genomic Determinants of Induction Failure and Persistent Prognostic Risk of FLT3-ITD in Pediatric Acute Myeloid Leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:58Z",
  "url": "https://research.draconitic.com/paper/ee2mj5j6bh0q2",
  "venue": "Cancers",
  "versions": []
}