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

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 pred...

Full description

Saved in:
Bibliographic Details
Main Authors: Yilan Xu, Danyang Li, Na Wang, Bei Ge, Chen Meng, Min Zhao, Zihan Lin, Min Li, Yigang Yuan, Yue Cai, Liuzhi Shi, Shenmeng Gao, Haige Ye
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Clinical Epigenetics
Subjects:
Online Access:https://doi.org/10.1186/s13148-025-01823-1
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823862013411983360
author Yilan Xu
Danyang Li
Na Wang
Bei Ge
Chen Meng
Min Zhao
Zihan Lin
Min Li
Yigang Yuan
Yue Cai
Liuzhi Shi
Shenmeng Gao
Haige Ye
author_facet Yilan Xu
Danyang Li
Na Wang
Bei Ge
Chen Meng
Min Zhao
Zihan Lin
Min Li
Yigang Yuan
Yue Cai
Liuzhi Shi
Shenmeng Gao
Haige Ye
author_sort Yilan Xu
collection DOAJ
description 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.
format Article
id doaj-art-f05a84c4f4294814b68e700f96547ff0
institution Kabale University
issn 1868-7083
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series Clinical Epigenetics
spelling doaj-art-f05a84c4f4294814b68e700f96547ff02025-02-09T12:42:51ZengBMCClinical Epigenetics1868-70832025-02-0117111310.1186/s13148-025-01823-1miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world settingYilan Xu0Danyang Li1Na Wang2Bei Ge3Chen Meng4Min Zhao5Zihan Lin6Min Li7Yigang Yuan8Yue Cai9Liuzhi Shi10Shenmeng Gao11Haige Ye12Department of Hematology, The First Affiliated Hospital of Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityHealth Care Center, The First Affiliated Hospital of Wenzhou Medical UniversityInfection Control Department, Eye Hospital, Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Clinical Medicine, Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract 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.https://doi.org/10.1186/s13148-025-01823-15-AzacytidineVenetoclaxDNA methylationAcute myeloid leukemia
spellingShingle Yilan Xu
Danyang Li
Na Wang
Bei Ge
Chen Meng
Min Zhao
Zihan Lin
Min Li
Yigang Yuan
Yue Cai
Liuzhi Shi
Shenmeng Gao
Haige Ye
miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting
Clinical Epigenetics
5-Azacytidine
Venetoclax
DNA methylation
Acute myeloid leukemia
title miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting
title_full miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting
title_fullStr miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting
title_full_unstemmed miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting
title_short miR-182 promoter hypermethylation predicts the better outcome of AML patients treated with AZA + VEN in a real-world setting
title_sort mir 182 promoter hypermethylation predicts the better outcome of aml patients treated with aza ven in a real world setting
topic 5-Azacytidine
Venetoclax
DNA methylation
Acute myeloid leukemia
url https://doi.org/10.1186/s13148-025-01823-1
work_keys_str_mv AT yilanxu mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT danyangli mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT nawang mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT beige mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT chenmeng mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT minzhao mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT zihanlin mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT minli mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT yigangyuan mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT yuecai mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT liuzhishi mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT shenmenggao mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting
AT haigeye mir182promoterhypermethylationpredictsthebetteroutcomeofamlpatientstreatedwithazaveninarealworldsetting