{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:48:08Z","timestamp":1792068488894,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82270177"],"award-info":[{"award-number":["No. 82270177"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["No. 2024AFB880"],"award-info":[{"award-number":["No. 2024AFB880"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute myeloid leukemia (AML) is a metabolically heterogeneous malignancy with poor outcomes and limited durable therapeutic options. We investigated NFS1, a key enzyme involved in iron\u2010sulfur cluster biogenesis, as a potential metabolic vulnerability in AML. NFS1 was overexpressed in AML samples, and higher expression was associated with inferior overall survival in the TCGA\u2010LAML cohort. Genetic knockdown of NFS1 markedly suppressed AML cell proliferation in vitro and reduced tumor growth in subcutaneous xenograft models. NFS1 knockdown induced disturbances in iron homeostasis accompanied by increased reactive oxygen species production and lipid peroxidation, together with reduced GPX4 expression. Together with the partial restoration of cell viability by ferrostatin\u20101, deferoxamine, and Z\u2010VAD\u2010FMK, these changes were consistent with concurrent apoptotic and ferroptosis\u2010like cell death. Transcriptomic analysis revealed enrichment of type I interferon\u2010related signaling pathways, while experimental validation demonstrated increased STAT1 phosphorylation at Tyr701 and increased expression of the downstream effector IFIT2. IFIT2 knockdown partially reversed the anti\u2010proliferative effects of NFS1 knockdown, supporting an association between the growth\u2010suppressive phenotype induced by NFS1 knockdown and STAT1\/IFIT2\u2010associated signaling. NFS1 knockdown was also accompanied by increased expression of PD\u2010L1 and elevated concentrations of inflammatory cytokines such as IL\u20106 and IL\u20108, and reduced CD80 expression in THP\u20101\u2010derived macrophage\u2010like cells in an in vitro co\u2010culture system. These findings indicate that NFS1 depletion is associated with immune\u2010related transcriptional and phenotypic changes in vitro. Furthermore, NFS1 knockdown enhanced the in vitro sensitivity of AML cells to azacitidine, venetoclax, and bortezomib. Collectively, this study suggests that NFS1 may represent a metabolic vulnerability in AML that links its depletion to iron dysregulation, apoptotic and ferroptosis\u2010like cell death, and STAT1\/IFIT2\u2010associated signaling, providing a rationale for further investigation of NFS1 as a potential therapeutic target in AML.<\/jats:p>","DOI":"10.1002\/hon.70277","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:57:52Z","timestamp":1792065472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NFS1 as a Metabolic Vulnerability in Acute Myeloid Leukemia Through Iron Dysregulation and STAT1\/IFIT2\u2010Associated Signaling"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6128-3857","authenticated-orcid":false,"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hematology Tongji Hospital Tongji Medical 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