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Miller Family Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R50-CA252135,P30CA033572"],"award-info":[{"award-number":["R50-CA252135,P30CA033572"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Research and Development Program of Zhejiang Province, China","award":["2024C03162"],"award-info":[{"award-number":["2024C03162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:p>Acute myeloid leukemia (AML) is an aggressive and often deadly malignancy associated with proliferative immature myeloid blasts. Here, we identified CD84 as a critical survival regulator in AML. High levels of CD84 expression provided a survival advantage to leukemia cells, whereas CD84 downregulation disrupted their proliferation, clonogenicity, and engraftment capabilities in both human cell lines and patient-derived xenograft cells. Critically, loss of CD84 also markedly blocked leukemia engraftment and clonogenicity in MLL-AF9 and inv(16) AML mouse models, highlighting its pivotal role as a survival factor across species. Mechanistically, CD84 regulated leukemia cells\u2019 energy metabolism and mitochondrial dynamics. Depletion of CD84 altered mitochondrial ultrastructure and function of leukemia cells, and it caused downmodulation of both oxidative phosphorylation and fatty acid oxidation pathways. CD84 knockdown induced a block of Akt phosphorylation and downmodulation of nuclear factor erythroid 2-related factor 2 (NRF2), impairing AML antioxidant defense. Conversely, CD84 overexpression stabilized NRF2 and promoted its transcriptional activation, thereby supporting redox homeostasis and mitochondrial function in AML. Collectively, our findings indicate that AML cells depend on CD84 to support antioxidant prosurvival pathways, highlighting a therapeutic vulnerability of leukemia cells.<\/jats:p>","DOI":"10.1172\/jci176818","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T12:04:03Z","timestamp":1744113843000},"source":"Crossref","is-referenced-by-count":12,"title":["Identification of CD84 as a potent survival factor in acute myeloid leukemia"],"prefix":"10.1172","volume":"135","author":[{"given":"Yinghui","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China."},{"name":"Judy and Bernard Briskin Center for Multiple Myeloma Research, Department of Hematology and Hematopoietic Cell Transplantation, and"},{"name":"Department of Hematologic 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