在真实世界中，miR-182启动子高甲基化预示着接受阿扎胞苷+维奈托克治疗的急性髓系白血病患者有更好的预后。

miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting.

作者信息

Xu Yilan, Li Danyang, Wang Na, Ge Bei, Meng Chen, Zhao Min, Lin Zihan, Li Min, Yuan Yigang, Cai Yue, Shi Liuzhi, Gao Shenmeng, Ye Haige

机构信息

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, 1 Xuefubei Street, Ouhai District, Wenzhou, 325000, Zhejiang Province, China.

Medical Research Center, The First Affiliated Hospital of Wenzhou Medical University, 1 Xuefubei Street, Ouhai District, Wenzhou, 325000, Zhejiang Province, China.

出版信息

Clin Epigenetics. 2025 Feb 5;17(1):18. doi: 10.1186/s13148-025-01823-1.

DOI:10.1186/s13148-025-01823-1

PMID:39910681

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11800541/

Abstract

BACKGROUND

5-Azacytidine (AZA) combined with the BCL2 inhibitor Venetoclax (VEN) is the standard treatment for elderly acute myeloid leukemia (AML) patients or those who are unfit for intensive chemotherapy (elderly or unfit AML). However, an effective and rapid predictive biomarker to predict treatment outcome remains elusive.

METHODS

miR-182 promoter methylation was measured in 94 AZA + VEN-treated elderly or unfit AML patients and 20 normal controls (NCs) samples. To determine whether miR-182 promoter methylation is a predictive marker of clinical outcomes in AZA + VEN-treated AML patients in a real-world setting, we analyzed and compared the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate, overall survival (OS), and leukemia free-survival (LFS) across different methylation groups: miR-182 promoter hypomethylation (median value < 20.21%) and hypermethylation (> 20.21%) in a retrospective study.

RESULTS

The average methylation frequency was markedly higher in 94 AZA + VEN-treated elderly or unfit AML patients than that in 20 NCs. However, some AML patients (11.7%) still presented low miR-182 promoter methylation (< 10%). The average time to obtain CR/CRi was shorter in AML patients with miR-182 promoter hypermethylation than AML with hypomethylation. Moreover, the median OS and LFS were longer in AML patients with miR-182 promoter hypermethylation than AML with hypomethylation. Finally, the area under the curve (AUC) for 1-year mortality was 0.831, for 2-year was 0.788, and for 3-year was 0.800.

CONCLUSIONS

AML patients with miR-182 promoter hypermethylation have better outcomes. miR-182 promoter methylation is a predictive biomarker for AZA + VEN-treated AML patients.

摘要

背景

5-氮杂胞苷（AZA）联合BCL2抑制剂维奈托克（VEN）是老年急性髓系白血病（AML）患者或不适合强化化疗患者（老年或不适合的AML）的标准治疗方案。然而，一种能有效快速预测治疗结果的生物标志物仍未找到。

方法

在94例接受AZA+VEN治疗的老年或不适合的AML患者及20例正常对照（NC）样本中检测miR-182启动子甲基化情况。为确定在真实临床环境中miR-182启动子甲基化是否为接受AZA+VEN治疗的AML患者临床结局的预测标志物，我们在一项回顾性研究中分析并比较了不同甲基化组（miR-182启动子低甲基化（中位值<20.21%）和高甲基化（>20.21%））的完全缓解（CR）/伴有血液学不完全恢复的CR（CRi）率、总生存期（OS）和无白血病生存期（LFS）。

结果

94例接受AZA+VEN治疗的老年或不适合的AML患者的平均甲基化频率显著高于20例NC。然而，部分AML患者（11.7%）仍表现为低miR-182启动子甲基化（<10%）。miR-182启动子高甲基化的AML患者获得CR/CRi的平均时间短于低甲基化患者。此外，miR-182启动子高甲基化的AML患者的中位OS和LFS长于低甲基化患者。最后，1年死亡率的曲线下面积（AUC）为0.831，2年为0.788，3年为0.800。