The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia
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Le résumé fourni par la source
Acute myeloid leukemia (AML) develops within a bone marrow environment that influences leukemic stem cell behavior, residual disease, and response to therapy. This review examines evidence that the marrow microenvironment is not only a site of leukemic growth, but can actively shape AML initiation, maintenance, and treatment resistance. Clinical observations such as donor cell leukemia after allogeneic transplantation, together with experimental models in which stromal or osteolineage abnormalities induce myeloid disease, suggest that altered niches may contribute to leukemogenesis in selected settings. In established AML, vascular and endosteal compartments provide adhesive, chemokine, inflammatory, and metabolic signals that promote leukemic-cell retention, quiescence, survival, and chemotherapy tolerance. AML cells also remodel the surrounding marrow, suppressing normal hematopoiesis and generating stromal, endothelial, osteoblastic, adipocytic, and immune-cell programs that favor leukemic persistence. These interactions are especially relevant to drug resistance, including resistance to venetoclax-based therapy, where cytokine-mediated changes in apoptotic dependence, fatty-acid metabolism, mitochondrial adaptation, and stromal support may all contribute. Several therapeutic approaches have attempted to disrupt niche-mediated protection, including targeting CXCL12/CXCR4 signaling, adhesion pathways, inflammatory circuits, Hedgehog signaling, and metabolic dependencies. Although early-phase studies have shown activity in some AML subsets, randomized evidence remains limited and results have been inconsistent. We discuss how a better understanding of microenvironmental biology may help define when niche-directed therapy is most likely to complement conventional and molecularly targeted AML treatment.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia
- Date Crossref
- 27/07/2026
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Istituto Oncologico Veneto pays non établi dans la noticeÉtablissement de santé
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Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori pays non établi dans la noticeStructure de recherche
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University of Padua pays non établi dans la noticeUniversité ou école supérieure
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Veneto Institute of Oncology (IOV-IRCCS) Department of Oncology pays non établi dans la noticeStructure de recherche
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Biosciences Laboratory pays non établi dans la noticeStructure de recherche
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University of Padova Department of Pharmaceutical and Pharmacological Sciences pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine and Surgery pays non établi dans la noticeUniversité ou école supérieure
Istituto Oncologico Veneto, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori et University of Padua, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.