{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:32:12Z","timestamp":1789122732643,"version":"build-2803163510"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Development Plan Projects of Henan Province in 2024 \/ Henan Province Science and Technology Research Projects","award":["No. 242102310152"],"award-info":[{"award-number":["No. 242102310152"]}]},{"name":"Henan Province Medical Science and Technology Research Project (Joint Construction Program) in 2024","award":["No. LHGJ20240999"],"award-info":[{"award-number":["No. LHGJ20240999"]}]},{"name":"Key Project of Medical Science and Technology Research Program of Zhoukou Central Hospital in 2023","award":["No. 20230102"],"award-info":[{"award-number":["No. 20230102"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>PANoptosis is a newly defined form of programmed cell death that integrates features of apoptosis, pyroptosis and necroptosis, playing a critical role in immune regulation and tumor biology. Clinically, Acute Myeloid Leukemia (AML) patients with high DC\u2011STAMP expression exhibited notably poorer cytogenetic risk profiles and shorter overall survival. Gene set enrichment analysis of primary AML samples from public databases revealed significant enrichment of the mTORC1 signaling pathway, a core signaling axis regulating the apoptotic process, in AML samples with high DC-STAMP expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DC-STAMP knockdown and overexpression models were established in the AML cell line THP-1 using small interfering RNA (siRNA) and lentiviral plasmids, respectively. Western blotting and RT-PCR were used to assess changes in PI3K\/AKT\/mTOR pathway activity in response to altered DC-STAMP expression. Flow cytometry and other cellular phenotypic assays were employed to evaluate the impact of DC-STAMP on PANoptosis in AML cells. Finally, PI3K inhibitors were introduced to assess the functional reversal of DC-STAMP\u2013driven malignant phenotypes through downstream PI3K pathway inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High DC-STAMP expression in AML activated the PI3K\/AKT\/mTOR signaling pathway and suppressed the PANoptosis process, thereby enhancing leukemic cell survival and chemoresistance. In contrast, genetic silencing of DC-STAMP or pharmacological inhibition of downstream PI3K restored normal apoptotic processes and significantly attenuated the malignant phenotypes driven by mTOR hyperactivation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Activation of DC-STAMP is an essential mechanism that suppresses PANoptosis and promotes chemoresistance in AML cells. Targeting the downstream PI3K\/mTOR signaling pathway may offer a promising therapeutic strategy for this high-risk AML subtype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0339670","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:47:25Z","timestamp":1768589245000},"page":"e0339670","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["DC-STAMP activates the PI3K\/AKT\/mTOR signaling pathway to regulate PANoptosis in acute myeloid leukemia"],"prefix":"10.1371","volume":"21","author":[{"given":"Qian","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4569-2346","authenticated-orcid":true,"given":"Junying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"issue":"1","key":"pone.0339670.ref001","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13045-021-01062-w","article-title":"Emerging agents and regimens for AML","volume":"14","author":"H Liu","year":"2021","journal-title":"J Hematol Oncol"},{"issue":"3","key":"pone.0339670.ref002","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2174\/1568009616666151113120146","article-title":"Potential therapeutic approaches for the treatment of acute myeloid leukemia with AML1-ETO translocation","volume":"16","author":"R Arora","year":"2016","journal-title":"Curr Cancer Drug Targets"},{"issue":"15","key":"pone.0339670.ref003","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1182\/blood.2022018108","article-title":"Overlapping features of therapy-related and de novo NPM1-mutated AML","volume":"141","author":"J Othman","year":"2023","journal-title":"Blood"},{"issue":"1","key":"pone.0339670.ref004","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12964-023-01282-2","article-title":"The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: Immune checkpoints, metabolic checkpoints, and signaling pathways","volume":"21","author":"M Bakhtiyari","year":"2023","journal-title":"Cell Commun Signal"},{"issue":"7","key":"pone.0339670.ref005","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41417-024-00765-9","article-title":"PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment","volume":"31","author":"J Gao","year":"2024","journal-title":"Cancer Gene Ther"},{"issue":"11","key":"pone.0339670.ref006","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/s41594-020-0493-6","article-title":"Single-gene imaging links genome topology, promoter-enhancer communication and transcription control","volume":"27","author":"J Li","year":"2020","journal-title":"Nat Struct Mol Biol"},{"issue":"9","key":"pone.0339670.ref007","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1517\/14728220903136775","article-title":"Targeting the PI3K\/AKT\/mTOR signaling network in acute myelogenous leukemia","volume":"18","author":"AM Martelli","year":"2009","journal-title":"Expert Opin Investig Drugs"},{"key":"pone.0339670.ref008","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 signaling and the metabolic control of cell growth","volume":"45","author":"I Ben-Sahra","year":"2017","journal-title":"Curr Opin Cell Biol"},{"key":"pone.0339670.ref009","doi-asserted-by":"crossref","first-page":"876689","DOI":"10.3389\/fgene.2022.876689","article-title":"High Expression of DC-STAMP gene predicts adverse outcomes in AML","volume":"13","author":"Q Liang","year":"2022","journal-title":"Front Genet"},{"key":"pone.0339670.ref010","doi-asserted-by":"crossref","unstructured":"Simon DN, Rout MP. 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