{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:44:57Z","timestamp":1777484697146,"version":"3.51.4"},"reference-count":52,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"The First Hospital of Lanzhou University","award":["ldyyyn2018-64"],"award-info":[{"award-number":["ldyyyn2018-64"]}]},{"name":"The First Hospital of Lanzhou University","award":["ldyyyn2023-12"],"award-info":[{"award-number":["ldyyyn2023-12"]}]},{"name":"The Natural Science Foundation of Gansu Province","award":["18JR3RA356"],"award-info":[{"award-number":["18JR3RA356"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Control"],"published-print":{"date-parts":[[2025,8]]},"abstract":"\n Introduction<\/jats:title>\n \n Nucleophosmin 1 (\n NPM1<\/jats:italic>\n ), FMS-like tyrosine kinase 3-internal tandem duplication (\n FLT3-ITD<\/jats:italic>\n ), and de novo methyl transferase 3 A (\n DNMT3A<\/jats:italic>\n ) triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We explored the gene mutation spectrum and clinical characteristics of 165 AML patients retrospectively, particularly comparing patients with\n NPM1\/FLT3-ITD\/DNMT3A<\/jats:italic>\n triple-mutations and those without.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our results demonstrated significantly elevated white blood cell counts (\n P<\/jats:italic>\n < 0.001), bone marrow blast percentages (\n P<\/jats:italic>\n = 0.037), and platelet counts (\n P<\/jats:italic>\n = 0.007) in the triple-mutated cohort (6.7%) compared to the non-triple-mutated patients. Furthermore, all triple-mutated cases were classified as the M4\/M5 subtype of the French-American-British classification (\n P<\/jats:italic>\n = 0.017). Although no significant difference in complete remission rates was observed between the groups after initial treatment, the median overall survival for triple-mutated AML patients was only 4 months. Using the Gene Expression Omnibus (GEO) database and bioinformatics, we compared AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n mut\n <\/jats:sup>\n and AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n wt\n <\/jats:sup>\n . A total of 246 AML patients from the GEO dataset were included to evaluate the expression profiles of differentially expressed genes. The guanine nucleotide-binding protein subunit \u03b3 4 (\n GNG4<\/jats:italic>\n ) was differentially expressed between AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n mut\n <\/jats:sup>\n and AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n wt\n <\/jats:sup>\n , which had the most adjacent nodes among hub genes. The prognostic value of\n GNG4<\/jats:italic>\n was further validated in AML patient samples through qRT-PCR.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Clinical validation indicated a substantial downregulation of\n GNG4<\/jats:italic>\n in AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n mut\n <\/jats:sup>\n compared to AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n wt\n <\/jats:sup>\n patients. Thus,\n GNG4<\/jats:italic>\n may play a role in the low survival rate of AML\n \n NPM1<\/jats:italic>\n mut\n FLT3-ITD<\/jats:italic>\n mut\n DNMT3A<\/jats:italic>\n mut\n <\/jats:sup>\n patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/10732748251359836","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T04:16:37Z","timestamp":1752812197000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring\n NPM1\/FLT3-ITD\/DNMT3A<\/i>\n Triple Mutations and the Potential Prognostic Value of\n GNG4<\/i>"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8426-1797","authenticated-orcid":false,"given":"Yujie","family":"Niu","sequence":"first","affiliation":[{"name":"Lanzhou University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingchun","family":"Luo","sequence":"additional","affiliation":[{"name":"Xi\u2019an Central Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Lanzhou University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuancheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Lanzhou University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Lanzhou University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[{"name":"Lanzhou University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinli","family":"Jian","sequence":"additional","affiliation":[{"name":"Lanzhou University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Liu","sequence":"additional","affiliation":[{"name":"Lanzhou University"},{"name":"The First Hospital of Lanzhou 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