{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:33:40Z","timestamp":1791614020915,"version":"4.3.4"},"reference-count":19,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Nova Program of Science and Technology","award":["Z211100002121058"],"award-info":[{"award-number":["Z211100002121058"]}]},{"name":"Beijing Nova Program of Science and Technology","award":["BRWEP2024W134080106"],"award-info":[{"award-number":["BRWEP2024W134080106"]}]},{"name":"Beijing Nova Program of Science and Technology","award":["82100168"],"award-info":[{"award-number":["82100168"]}]},{"name":"Beijing Nova Program of Science and 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Funds","award":["0107050"],"award-info":[{"award-number":["0107050"]}]},{"name":"Peking University People\u2019s Hospital Research and Development Funds","award":["RS2020-03"],"award-info":[{"award-number":["RS2020-03"]}]},{"name":"Peking University People\u2019s Hospital Research and Development Funds","award":["RDY2020-29"],"award-info":[{"award-number":["RDY2020-29"]}]},{"name":"Peking University People\u2019s Hospital Research and Development Funds","award":["BMU2021PYB005"],"award-info":[{"award-number":["BMU2021PYB005"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["Z211100002121058"],"award-info":[{"award-number":["Z211100002121058"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["BRWEP2024W134080106"],"award-info":[{"award-number":["BRWEP2024W134080106"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["82100168"],"award-info":[{"award-number":["82100168"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["0107050"],"award-info":[{"award-number":["0107050"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["RS2020-03"],"award-info":[{"award-number":["RS2020-03"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["RDY2020-29"],"award-info":[{"award-number":["RDY2020-29"]}]},{"name":"Peking University Medicine Fund of Fostering Young Scholars\u2019 Scientific &amp; Technological Innovation","award":["BMU2021PYB005"],"award-info":[{"award-number":["BMU2021PYB005"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["Z211100002121058"],"award-info":[{"award-number":["Z211100002121058"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["BRWEP2024W134080106"],"award-info":[{"award-number":["BRWEP2024W134080106"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["82100168"],"award-info":[{"award-number":["82100168"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["0107050"],"award-info":[{"award-number":["0107050"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["RS2020-03"],"award-info":[{"award-number":["RS2020-03"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["RDY2020-29"],"award-info":[{"award-number":["RDY2020-29"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["BMU2021PYB005"],"award-info":[{"award-number":["BMU2021PYB005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The role of KDM6A gene mutations in acute myeloid leukemia (AML) remains poorly understood. This study aimed to evaluate the impact of KDM6A mutations on relapse risk, cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) in adult AML patients, with a particular focus on those with RUNX1::RUNX1T1 fusion. Methods: the retrospective analysis was conducted on 1970 adult AML patients treated at Peking University People\u2019s Hospital. Of these, 1676 patients who achieved complete remission (CR) were included. Among them, 27 harbored KDM6A mutations. Propensity score matching (PSM) was used (1:10 ratio) to compare outcomes between patients with and without KDM6A mutations. Further analysis focused on 207 patients with RUNX1::RUNX1T1 fusion, among whom 13 had KDM6A mutations (PSM 1:5). Results: In the overall cohort, KDM6A variants (n = 27) had a higher 2-year CIR (45.7% vs. 28.6%, p = 0.04). Fine\u2013Gray analysis showed KDM6A variants independently increased relapse risk (HR = 1.98 [1.08\u20133.63], p = 0.03). KDM6A mutations were associated with inferior 2-year RFS (36.3% vs. 60.9%, p = 0.044). Multivariable analysis confirmed KDM6A mutations as independent predictors of poor RFS (HR = 3.08 [1.56\u20136.08], p = 0.001). Among RUNX1::RUNX1T1 patients, KDM6A mutations significantly increased relapse risk (75.0% vs. 21.7%, p &lt; 0.001), raised 2-year CIR (46.9% vs. 24.0%, p = 0.05), worsened 2-year RFS (31.3% vs. 71.9%, p &lt; 0.001), and lowered 2-year OS (63.3% vs. 86.4%, p = 0.002). They were also independent predictors of CIR (HR = 2.46 [1.11\u20135.47], p = 0.03), RFS (HR = 5.1, [2.5\u201310.5], p &lt; 0.001) and OS (HR = 12.9, [4.3\u201338.7], p &lt; 0.001). Conclusions: KDM6A mutations are significantly associated with increased relapse risk and poor prognosis in AML, especially in patients with RUNX1::RUNX1T1 fusion, and may serve as a valuable prognostic biomarker.<\/jats:p>","DOI":"10.3390\/cancers17132236","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T09:57:39Z","timestamp":1751536659000},"page":"2236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["KDM6A Variants Increased Relapse Risk in Adult Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7531-1528","authenticated-orcid":false,"given":"Yijing","family":"Zhao","sequence":"first","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liting","family":"Niu","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanping","family":"Xu","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Huang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-0522","authenticated-orcid":false,"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"},{"name":"Department of Hematology, Peking University People\u2019s Hospital, Qingdao 266111, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-9887","authenticated-orcid":false,"given":"Feifei","family":"Tang","sequence":"additional","affiliation":[{"name":"Peking University People\u2019s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. 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