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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Hematologic Malignancies

Dominant TET2 Mutations Predict adverse Prognosis in Cytogenetically Normal Acute Myeloid Leukemia Patients

Provisionally accepted
Zhuanghui HaoZhuanghui Hao1Jingjing XiaJingjing Xia1,2Sicheng BianSicheng Bian3Miaoke SongMiaoke Song1Miao ZhangMiao Zhang1Jingyi FengJingyi Feng1硕 李硕 李1Huichao WangHuichao Wang1Yaofang ZhangYaofang Zhang1Wanfang YangWanfang Yang4Jianmei ChangJianmei Chang1Fanggang RenFanggang Ren1Xufeng HuangXufeng Huang5Xiuhua ChenXiuhua Chen1*Hongwei WangHongwei Wang1
  • 1Department of Hematology, Second Hospital of Shanxi Medical University, Taiyuan, China
  • 2Shanxi Medical University, Taiyuan, China
  • 3Department of Medicine, MetroHealth System, Case Western Reserve University, Cleveland, Cleveland, United States
  • 4Shanxi University of Chinese Medicine, Taiyuan, China
  • 5Department of Data Visualization, Faculty of Informatics, University of Debrecen, Debrecen, Hungary, Debrecen, Hungary

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Objective:This study aimed to characterize TET2 mutations in CN-AML, assess their clinical features, and evaluate the prognostic impact of VAF and clonal hierarchy on overall survival (OS) and relapse-free survival (RFS). Methods: A cohort of 206 adult CN-AML patients was analyzed for the presence of TET2 mutation characteristics, variant allele frequency (VAF) and clonal status. Clinical and prognostic implications were evaluated through survival analyses and validated by the Beat AML public database. Results: TET2 mutations were detected in 18.9% of CN-AML patients, with a median age of 55 years, significantly older than TET2 wild-type patients (P < 0.001). OS and RFS were no difference in the high-VAF group and low-VAF group. Patients with dominant TET2 mutations exhibited significantly shorter OS and RFS compared to subclonal group (P < 0.05). Multivariate Cox regression identified dominant TET2 mutations as an independent adverse prognostic factor for OS (HR = 2.026,P = 0.039). A nomogram model based on these findings demonstrated robust predictive performance (AUC = 0.735) and was validated by the Beat AML database. Conclusions: The prognostic impact of TET2 mutations is not determined by VAF, but rather by TET2 clonal dominance and the interplay between mutations within the same clone.

Keywords: Acute Myeloid Leukemia, co-mutations, Dominant, Outcome, TET2 mutation, variant allele frequency

Received: 23 Oct 2025; Accepted: 12 Dec 2025.

Copyright: © 2025 Hao, Xia, Bian, Song, Zhang, Feng, 李, Wang, Zhang, Yang, Chang, Ren, Huang, Chen and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xiuhua Chen

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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