{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:50:45Z","timestamp":1782237045912,"version":"3.54.5"},"reference-count":136,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Myelodysplastic syndromes are clonal hematopoietic neoplasms in which ineffective hematopoiesis arises within the context of chronic inflammation and immune dysregulation. Growing evidence indicates that aging-associated inflammaging and inflammation-driven remodeling of the bone marrow microenvironment are not secondary phenomena, but active forces that shape clonal selection, lineage commitment, and disease evolution. This narrative review integrates recent insights from translational immunology, stem cell biology, multi-omics analyses, and clinical studies to examine the reciprocal interplay between inflammation and myelodysplastic syndrome pathogenesis. Chronic inflammatory stress imposes selective pressure on hematopoietic stem cells, favoring the expansion of mutation-bearing clones characteristic of clonal hematopoiesis and overt disease. As inflammation persists, immune dysfunction, together with stromal alterations, progressively reinforce ineffective hematopoiesis and clonal dominance. Genetic lesions, including TP53 and spliceosome mutations, further amplify inflammatory signaling and reshape the marrow niche, conferring clonal fitness and genomic instability. Clinically, readily accessible peripheral blood inflammatory indices reflect these biological processes and correlate with prognosis and therapeutic response. Collectively, these observations position inflammation as a unifying determinant of myelodysplastic syndrome initiation, progression, and treatment sensitivity. Integrating inflammatory signatures with genomic profiling may refine risk stratification and support the development of therapeutic strategies aimed at restoring marrow homeostasis and limiting inflammation-driven clonal evolution.<\/jats:p>","DOI":"10.3390\/cells15131137","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:11:49Z","timestamp":1782234709000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Signatures in MDS: The Missing Link Between Genetics, Microenvironment, and Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Adele","family":"Bottaro","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisa","family":"Nasso","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mirabile","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-2640","authenticated-orcid":false,"given":"Manlio","family":"Fazio","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-8239","authenticated-orcid":false,"given":"Alessandro","family":"Allegra","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1182\/blood.2023020078","article-title":"Diagnosis and classification of myelodysplastic syndromes","volume":"142","author":"Hasserjian","year":"2023","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vallelonga, V., Gandolfi, F., Ficara, F., Della Porta, M.G., and Ghisletti, S. 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