{
  "abstract": "Introduction: Resistance to tyrosine kinase inhibitors (TKIs) remains a major cause of treatment failure in chronic myeloid leukemia (CML). This study investigated the role of ribosomal protein S3 (RPS3) in TKI resistance and its association with NF-κB signaling.\n\nMethods: Exploratory RNA sequencing and an RNA-binding protein database were used to prioritize a candidate for subsequent clinical expression and functional analyses. RPS3 expression was examined in an independent clinical cohort and resistant cell models. RPS3 knockdown and pharmacological modulation were used to evaluate drug sensitivity, apoptosis, cell cycle distribution, and NF-κB-associated signaling.\n\nResults: RPS3 was upregulated in clinical samples from patients with TKI resistance or poor responses and in resistant cell models. Receiver operating characteristic analysis showed that RPS3 expression discriminated between resistant/poor-response patients and good responders in the validation cohort. RPS3 knockdown lowered imatinib and nilotinib IC ₅₀ values, with increased apoptosis and G ₀ /G ₁ -phase arrest following TKI exposure. These effects were accompanied by reduced p65 phosphorylation, a lower p65 nuclear/cytoplasmic fluorescence ratio, and decreased MCL-1 and BCL-XL mRNA levels. TNF-α treatment increased TKI tolerance and reduced TKI-induced apoptosis in RPS3-knockdown cells, whereas co-treatment with BAY-11-7082 counteracted these effects. BAY-11-7082 also showed synergistic inhibitory effects with TKIs in resistant cells under the highest single agent model.\n\nDiscussion: These findings identify RPS3 as a contributor to TKI resistance in CML cell models and connect its functional effects to NF-κB-associated anti-apoptotic signaling. By integrating clinical expression data with functional and pharmacological analyses, this study supports further investigation of RPS3 as a candidate target for sensitizing resistant CML cells to TKIs.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Molecular Diagnosis and Treatment of Hematological Diseases of Shanxi Province, Department of Hematology, The Second Hospital of Shanxi Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zheng Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Sijin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxin Ning"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinwen Dang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhuanghui Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoning Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Bianbian Qiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Qianni Jin"
    },
    {
      "affs": [
        0
      ],
      "name": "Kai Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Congrui Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhilei Jin"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongwei Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhifang Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/echcg64heg5cf.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.2005945",
  "fulltext_url": null,
  "id": "echcg64heg5cf",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.2005945/full",
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/echcg64heg5cf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "10.3389/fonc.2026.2005945",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.2005945/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "Role and mechanism of ribosomal protein S3 in tyrosine kinase inhibitor resistance in chronic myeloid leukemia",
  "title_text": "Role and mechanism of ribosomal protein S3 in tyrosine kinase inhibitor resistance in chronic myeloid leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:21:08Z",
  "url": "https://research.draconitic.com/paper/echcg64heg5cf",
  "venue": "Frontiers in Oncology",
  "versions": []
}