{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:04:27Z","timestamp":1788354267769,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH222"],"award-info":[{"award-number":["ZR2021MH222"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81602087"],"award-info":[{"award-number":["81602087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The human immunodeficiency virus type I enhancer binding protein (<jats:italic>HIVEP<\/jats:italic>) family, which contains zinc finger and acid\u2010rich (ZAS) domains, has been demonstrated to be implicated in vital biological processes, such as cell survival, tumor necrosis factor (TNF) signaling, and tumor formation. However, its expression patterns, prognostic relevance, and functional implications in acute myeloid leukemia (AML) remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We inspected <jats:italic>HIVEP<\/jats:italic> mRNA expression levels in datasets from The Cancer Genome Atlas (TCGA) and GSE24006. Survival analyses were orchestrated using the web\u2010based bioinformatics platforms and R studio in two AML cohorts. Prognostic value and capacity were assessed by Cox regression analyses. Association of <jats:italic>HIVEP3<\/jats:italic> expression levels with clinical characteristics were analyzed with R and UALCAN. Subsequentially, functional enrichment analyses were operated to interpret <jats:italic>HIVEP3<\/jats:italic> co\u2010expressed gene clusters. A prognostic gene signature was created by the least absolute shrinkage and selection operator (LASSO) regression algorithm. Moreover, bone marrow aspirate smears of AML patients were stained for <jats:italic>HIVEP3<\/jats:italic> by immunohistochemistry (IHC). <jats:italic>HIVEP3<\/jats:italic> expression was examined by qRT\u2010PCR in leukemia cell lines treated with ferroptosis compounds in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Augmented transcriptional levels of <jats:italic>HIVEP2<\/jats:italic> and <jats:italic>3<\/jats:italic> were noted in AML patients (<jats:italic>p<\/jats:italic>&lt;0.001). <jats:italic>HIVEP3<\/jats:italic> not only could confer adverse prognosis independently in AML patients, but also was associated with AML subtypes, age, cytogenetic risk, and disease\u2010related molecules. Co\u2010expressed gene clusters of <jats:italic>HIVEP3<\/jats:italic> were enriched in functional pathways related to AML leukemogenesis, such as ribosome, metabolism, and calcium signaling. Combined with multiple tumorigenesis signaling pathways, we proposed an integrated LASSO model with <jats:italic>HIVEP3<\/jats:italic> and ferroptosis regulators <jats:italic>AIFM2<\/jats:italic> and <jats:italic>LPCAT3<\/jats:italic>, to predict the outcome for AML patients. Furthernore, altered <jats:italic>HIVEP3<\/jats:italic> expression at the mRNA or protein level was confirmed in sorted leukemia cells and blast cells in bone marrow tissues. In vitro experiments authenticated the involvement of <jats:italic>HIVEP3<\/jats:italic> in ferroptosis signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that <jats:italic>HIVEP3<\/jats:italic> is a de novo independent prognostic indicator, and the crosstalk between <jats:italic>HIVEP3<\/jats:italic> and ferroptosis signaling pathways may inspire a specific perspective on the oncological network of AML.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4806","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T10:34:59Z","timestamp":1652178899000},"page":"5050-5065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp><i>HIVEP3<\/i><\/scp> cooperates with ferroptosis gene signatures to confer adverse prognosis in acute myeloid leukemia"],"prefix":"10.1002","volume":"11","author":[{"given":"Xiaoning","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine  Jinan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrotic The Fifth People's Hospital of Jinan  Jinan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine  Jinan PR 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