{
  "abstract": "Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy in which chemoresistance and relapse, often driven by leukemia stem cells (LSCs), remain major obstacles to cure. Autophagy is an evolutionarily conserved lysosomal degradation pathway whose function in AML is not fixed but is stage- and context-dependent: it restrains leukemogenesis in some settings while sustaining established and therapy-stressed LSCs in others. The Bcl-2-associated athanogene 3 (BAG3)-heat shock protein 70 (HSP70) axis integrates proteotoxic stress with the autophagy machinery, most notably through chaperone-assisted selective autophagy (CASA). This review applies a four-tier evidence framework-direct AML evidence, other hematological evidence, non-AML evidence, and proposed or hypothetical mechanisms-and explicitly separates BAG3-specific evidence from general HSP70 and autophagy findings. Direct AML evidence is comparatively strong for the cytoprotective, mitophagic and chemoresistance roles of autophagy and HSP70, but it is limited for a specific BAG3 dependency. In particular, direct BAG3 coupling to ULK1, competitive BAG3/HSP70 binding at the Beclin1 BH3 domain, and direct HSP70 shielding of ATG5 from cleavage are not supported by primary evidence. We examine the crosstalk between this axis and recurrent AML alterations (FLT3-ITD, NPM1 and TP53), and survey therapeutic strategies ranging from ATP-site HSP70 inhibitors to HSP70-BAG3 protein-protein interaction inhibitors, dual HSP70/HSP90 targeting, BAG3-directed agents, targeted protein degradation, nanoparticle delivery and emerging immunotherapies. We stratify direct axis-targeting from broad HSP70-family or proteostasis approaches. Finally, we summarize the principal knowledge gaps and the potential therapeutic window, cardiac-safety and biomarker challenges that must be addressed to convert the BAG3-HSP70 axis from a plausible mechanism into a precision target in AML.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hematology, People's Liberation Army Joint Logistics Support Force 940th Hospital, Lanzhou, China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yang Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Tao Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aa0agrvtxd6be.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1980188",
  "fulltext_url": "https://europepmc.org/articles/PMC13714359",
  "id": "aa0agrvtxd6be",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953017",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7221762008",
  "pdf_url": "https://europepmc.org/articles/PMC13714359?pdf=render",
  "pmcid": "PMC13714359",
  "pmid": "42953017",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/aa0agrvtxd6be.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953017",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953017"
    },
    {
      "first_seen": "2026-11-01T12:21:52Z",
      "native_id": "PMC13714359",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1980188"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Research progress on the BAG3-HSP70 axis-mediated autophagy in acute myeloid leukemia.",
  "title_text": "Research progress on the BAG3-HSP70 axis-mediated autophagy in acute myeloid leukemia.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:52Z",
  "url": "https://research.draconitic.com/paper/aa0agrvtxd6be",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}