Evidence map›Paper›PMID 40409464›Full record

ArticleJournal of advanced research2026

Dynamic heterogeneity towards drug resistance in AML cells is primarily driven by epigenomic mechanism unveiled by multi-omics analysis.

Yulong Zhang, Yanfang Lu, Liyao Mai, Zebin Wen, Min Dai, Siwen Xu, Xianwei Lin, Yongjian Luo, Yinbin Qiu, Yuting Chen and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Yulong ZhangDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China; Precision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China.
Yanfang LuDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China; Department of Nephrology, Henan Provincial Key Laboratory of Kidney Disease and Immunology, Henan International Joint Laboratory of Kidney Disease and Microenvironment, Henan Provincial Clinical Research Center for Kidney Disease, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Henan 450053, China.
Liyao MaiDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China; Key Laboratory of Conservation and Application in Biodiversity of South China, School of Life Sciences, Guangzhou University, Guangzhou, Guangdong, China.
Zebin WenDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China.
Min DaiInstitute of Genetics and Developmental Biology, Innovation Academy of Seed Design, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
Siwen XuDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China.
Xianwei LinSequMed Institute of Biomedical Sciences, Guangzhou 510530 Guangdong Province, China.
Yongjian LuoSequMed Institute of Biomedical Sciences, Guangzhou 510530 Guangdong Province, China.
Yinbin QiuDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China.
Yuting ChenDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China; Precision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China.
Zhanying DongDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China.
Caiming ChenDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China; Precision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China.
Wei MengDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China.
Xingguang LuoDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.
Guanchuan LinDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China. Electronic address: lyncelot.lin@qq.com.
Paul K H TamPrecision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China. Electronic address: pkhtam@must.edu.mo.
Xinghua PanDepartment of Biochemistry and Molecular Biology, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, School of Basic Medical Sciences, Guangzhou, Guangdong, China; Precision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; Key Laboratory of Infectious Diseases Research in South China (China Ministry Education), Southern Medical University, Guangzhou, Guangdong 510515, China; Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, Guangdong Province 510515, China. Electronic address: panxinghua@must.edu.mo.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAcute myeloid leukemia (AML) is a hematologic malignancy characterized by aggressive proliferation and chemoresistance, leading to poor patient outcomes. Despite advances in chemotherapy, resistance mechanisms remain inadequately understood, particularly at the cellular and molecular level.

objectivesThis study aims to elucidate the cellular and molecular mechanisms underlying drug resistance in AML cells.

methodsA multi-omics approach was employed, integrating single-cell RNA sequencing (scRNA-seq), chromatin accessibility profiling (scATAC-seq), DNA methylation analysis, and whole-exome sequencing (WES). AML cell lines (KG-1a, Kasumi-1, and HL-60) were treated with standard chemotherapeutic agents, including cytarabine (Ara-C), daunorubicin (DNR), azacitidine (AZA), and decitabine (DEC). Additionally, we developed a novel multiplexed scRNA-seq strategy, NAMUL-seq, to enhance the efficiency and scalability of single-cell transcriptomic research.

resultsWe observed substantial cellular heterogeneity and dynamic transcriptomic trajectories in AML cells subjected to various treatments, uncovering a tendency for reprogramming towards a more stem-like state. Notably, Ara-C-resistant KG-1a cells predominantly originated from G2/M phase subpopulations, suggesting a resistance mechanism linked to specific cell cycle stages. Our findings further indicate that rapid Ara-C resistance is primarily driven by epigenomic changes, including alterations in DNA methylation, chromatin architecture, and transcription factor activity, whereas exonic mutations played a minimal role.

conclusionThis study demonstrates that AML drug resistance is predominantly driven by epigenomic mechanisms rather than genetic mutations. This study provides a detailed cellular and molecular characterization of AML drug response and resistance, identifying potential therapeutic targets and laying the groundwork for future efforts to overcome chemoresistance.

Indexed as

Drug Resistance, NeoplasmLeukemia, Myeloid, AcuteAntineoplastic AgentsCell Line, TumorDNA MethylationEpigenomicsExome SequencingHumansMultiomicsSingle-Cell AnalysisTranscriptomeAntineoplastic AgentsAcute myeloid leukemiaDrug resistanceMulti-omicsSample multiplexingSingle-cell sequencing

Identifiers

PMID40409464
PMCPMC12869214

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.