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Inflammation shapes hematopoietic stem and progenitor cell fate across this spectrum, yet its network organization, genetic conditioning, and therapeutic implications remain incompletely defined. An integrative, literature-based analysis of inflammatory cytokines, genetic contexts, and therapeutic targeting across major BMF disorders, including inherited BMF syndromes, aplastic anemia (AA), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and myelofibrosis (MF). Gene\u2013inflammation\u2013outcome networks and co-occurrence maps were constructed with stratification by germline and somatic alterations. Therapeutic activity was mapped across cytokine-directed and pathway-targeted agents. Inflammatory signaling emerged as a conserved feature across all BMF categories, with TNF-\u03b1, IFN-\u03b3, and IL-6 forming a recurrent core module, and TGF-\u03b2 linking inflammatory programs to fibrotic remodeling. TP53- and JAK2-associated pathways appeared as central nodes integrating multi-cytokine inputs. Germline lesions in FANCA, TERC\/TERT, and GATA2 were predominantly associated with apoptotic stem-cell attrition. In contrast, somatic drivers, including TP53, JAK2, TET2, DNMT3A, and ASXL1, were more frequently associated with clonal expansion. Multi-cytokine convergence on shared effectors was common, suggesting pathway redundancy. The therapeutic literature predominantly focused on TNF-\u03b1\/IFN-\u03b3\/IL-6 pathways, with comparatively limited exploration of TGF-\u03b2, IL-8, and IL-17. These findings support a role for inflammation as a unifying, context-dependent modifier across the BMF spectrum, and highlight TP53- and JAK2-centered circuitry as potential nodes for rational combination strategies. TGF-\u03b2, IL-8, and IL-17 axes and inherited BMF entities represent underexplored opportunities for biomarker-guided cytokine-directed intervention.<\/jats:p>","DOI":"10.31083\/fbl50689","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Network Architecture Across Bone Marrow Failure: An Immune-Genetic Continuum"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1450-2557","authenticated-orcid":true,"given":"Swarna","family":"Beesetti","sequence":"first","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Savage SA, Dufour C. 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