Background/Objectives: The role ofKDM6Agene mutations in acute myeloid leukemia (AML) remains poorly understood. This study aimed to evaluate the impact ofKDM6Amutations 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 withRUNX1::RUNX1T1fusion.Methods: the retrospective analysis was conducted on 1970 adult AML patients treated at Peking University People’s Hospital. Of these, 1676 patients who achieved complete remission (CR) were included. Among them, 27 harboredKDM6Amutations. Propensity score matching (PSM) was used (1:10 ratio) to compare outcomes between patients with and withoutKDM6Amutations. Further analysis focused on 207 patients withRUNX1::RUNX1T1fusion, among whom 13 hadKDM6Amutations (PSM 1:5).Results: In the overall cohort,KDM6Avariants (n= 27) had a higher 2-year CIR (45.7% vs. 28.6%,p= 0.04). Fine–Gray analysis showedKDM6Avariants independently increased relapse risk (HR = 1.98 [1.08–3.63],p= 0.03).KDM6Amutations were associated with inferior 2-year RFS (36.3% vs. 60.9%,p= 0.044). Multivariable analysis confirmedKDM6Amutations as independent predictors of poor RFS (HR = 3.08 [1.56–6.08],p= 0.001). AmongRUNX1::RUNX1T1patients,KDM6Amutations significantly increased relapse risk (75.0% vs. 21.7%,p< 0.001), raised 2-year CIR (46.9% vs. 24.0%,p= 0.05), worsened 2-year RFS (31.3% vs. 71.9%,p< 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 [1.11–5.47],p= 0.03), RFS (HR = 5.1, [2.5–10.5],p< 0.001) and OS (HR = 12.9, [4.3–38.7],p< 0.001).Conclusions:KDM6Amutations are significantly associated with increased relapse risk and poor prognosis in AML, especially in patients withRUNX1::RUNX1T1fusion, and may serve as a valuable prognostic biomarker.
背景/目的：KDM6A基因突变在急性髓系白血病（AML）中的作用尚不明确。本研究旨在评估KDM6A突变对成人AML患者复发风险、累积复发率（CIR）、无复发生存期（RFS）和总生存期（OS）的影响，尤其关注RUNX1::RUNX1T1融合基因阳性患者。 方法：对北京大学人民医院收治的1970例成人AML患者进行回顾性分析，其中1676例达到完全缓解（CR）的患者纳入研究，其中27例携带KDM6A突变。采用倾向性评分匹配（PSM，1:10比例）比较KDM6A突变组与无突变组的临床结局。进一步对207例RUNX1::RUNX1T1融合基因阳性患者进行分析，其中13例携带KDM6A突变（PSM 1:5）。 结果：在总体队列中，KDM6A突变组（n=27）的2年CIR显著更高（45.7% vs. 28.6%，p=0.04）。Fine-Gray分析显示KDM6A突变是复发风险的独立危险因素（HR=1.98 [1.08–3.63]，p=0.03）。KDM6A突变与较差的2年RFS相关（36.3% vs. 60.9%，p=0.044）。多变量分析证实KDM6A突变是RFS不良的独立预测因子（HR=3.08 [1.56–6.08]，p=0.001）。在RUNX1::RUNX1T1阳性患者中，KDM6A突变显著增加复发风险（75.0% vs. 21.7%，p<0.001），提高2年CIR（46.9% vs. 24.0%，p=0.05），降低2年RFS（31.3% vs. 71.9%，p<0.001）和2年OS（63.3% vs. 86.4%，p=0.002）。同时，KDM6A突变是CIR（HR=2.46 [1.11–5.47]，p=0.03）、RFS（HR=5.1 [2.5–10.5]，p<0.001）和OS（HR=12.9 [4.3–38.7]，p<0.001）的独立预测因子。 结论：KDM6A突变与AML患者复发风险增加及不良预后显著相关，尤其在RUNX1::RUNX1T1融合基因阳性患者中，可能成为有价值的预后生物标志物。
KDM6AVariants Increased Relapse Risk in Adult Acute Myeloid Leukemia
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