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Extensive research has elucidated the broad spectrum of biological mechanisms contributing to the development of AML and specifically characterized a variety of genetic alterations initiating and defining the disease. However, the role of inflammation in the pathogenesis of AML remains relatively unexplored; indeed, studies on the contribution of inflammatory signaling to disease initiation in myeloid malignancies have only recently gained attention, marking an emerging area of research. AML has the highest incidence in the elderly, where inflammation plays an even greater role. A granular understanding of inflammatory processes driving leukemogenesis thus promises to guide therapeutic strategies for a patient population where outcomes remain dismal. This review offers a comprehensive synthesis of the current knowledge on the role of inflammatory signaling in AML pathogenesis. It discusses the role of inflammation from premalignant states through malignant transformation, dissecting phenotypic, correlative studies from mechanistic evidence. We thereby highlight questions requiring further research to exploit the translational potential of therapies targeting inflammatory signaling and to address challenges with current immune\u2010modulating treatments. A particular focus is placed on assessing the role of inflammation in the interplay with genetic events as established factors in disease initiation and progression to clarify the current understanding of inflammatory signaling in AML pathogenesis.<\/jats:p>","DOI":"10.1002\/hem3.70188","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T19:23:52Z","timestamp":1755113032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inflammatory signaling in the pathogenesis of acute myeloid leukemia"],"prefix":"10.1002","volume":"9","author":[{"given":"Artemis Margrith","family":"Baumann","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Zurich Zurich Switzerland"},{"name":"Department of Medical Oncology and Hematology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-4227","authenticated-orcid":false,"given":"Jana Maria","family":"Ellegast","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Zurich Zurich Switzerland"},{"name":"Department of Medical Oncology and Hematology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040690208"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.127.3.455"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022222"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406184"},{"key":"e_1_2_12_6_1","unstructured":"SEER*Explorer: an interactive website for SEER cancer statistics. 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