{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:07:05Z","timestamp":1778101625467,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Current prognostic stratification for acute myeloid leukemia (AML) patients primarily relies on international guidelines such as ELN 2022. However, these guidelines provide limited explicit guidance on how to comprehensively assess prognosis when patients harbor concurrent multiple gene mutations, potentially leading to inaccurate risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study enrolled 299 adult AML patients (median age: 53.5\u00a0years). Clinical features, mutation status of prognosis-related genes, complete remission (CR) rate after two induction courses, and overall survival (OS) were analyzed. Logistic regression and Cox proportional hazards models were employed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study cohort, the incidence rates of\n                      <jats:italic>NRAS<\/jats:italic>\n                      and CEBPA single mutations were 15.38% (46\/299) and 13.37% (40\/299), respectively, while the\n                      <jats:italic>NRAS<\/jats:italic>\n                      and\n                      <jats:italic>CEBPA<\/jats:italic>\n                      co-mutation rate was 4.68% (14\/299). Both univariate and multivariate logistic regression analyses demonstrated that\n                      <jats:italic>CEBPA<\/jats:italic>\n                      mutation (OR = 2.807, 95% CI: 1.244\u20136.333,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.013) and\n                      <jats:italic>NRAS<\/jats:italic>\n                      mutation (OR = 4.028, 95% CI: 1.760\u20139.219,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.001) were independent positive predictive factors for achieving complete remission after two treatment courses. Survival analysis indicated that neither\n                      <jats:italic>NRAS<\/jats:italic>\n                      single mutation (HR = 1.11, 95% CI: 0.60\u20132.04,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.738) nor\n                      <jats:italic>CEBPA<\/jats:italic>\n                      single mutation (HR = 0.70, 95% CI: 0.36\u20131.34,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.280) was significantly associated with overall survival. Notably,\n                      <jats:italic>NRAS<\/jats:italic>\n                      and\n                      <jats:italic>CEBPA<\/jats:italic>\n                      co-mutation was confirmed as an independent adverse prognostic factor, conferring a 3.15-fold increased risk of death (HR = 3.15, 95% CI: 1.08\u20139.21,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.036) compared to patients without either mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>NRAS<\/jats:italic>\n                      and\n                      <jats:italic>CEBPA<\/jats:italic>\n                      co-mutation defines a distinct molecular subtype with independently poor prognosis in AML. Routine\n                      <jats:italic>NRAS<\/jats:italic>\n                      mutation screening in patients with\n                      <jats:italic>CEBPA<\/jats:italic>\n                      -mutated AML is warranted to refine risk stratification, particularly for identifying this high-risk subgroup, which may benefit from more intensive or novel therapeutic approaches.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1775927","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:00:45Z","timestamp":1773817245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic adverse prognosis of CEBPA and NRAS co-mutation in acute myeloid leukemia: a retrospective cohort study"],"prefix":"10.3389","volume":"14","author":[{"given":"Fujun","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxu","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nian","family":"Liu","sequence":"additional","affiliation":[{"name":"Health Management Center, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital of Guilin Medical University","place":["Guilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1177\/030089168106700308","article-title":"Therapy of acute nonlymphocytic leukemia in children: a review of 73 patients","volume":"67","author":"Amadori","year":"1981","journal-title":"Tumori"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1182\/blood-2007-05-091215","article-title":"Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients","volume":"111","author":"Bacher","year":"2008","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.3390\/cancers15133512","article-title":"Modern risk stratification of acute myeloid leukemia in 2023: integrating established and emerging prognostic factors","volume":"15","author":"Boscaro","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1073\/pnas.1324297111","article-title":"Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission","volume":"111","author":"Corces-Zimmerman","year":"2014","journal-title":"Proc. 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