Evidence mapPaperPMID 40796730Full record

ArticleCell death & disease2025

The ALDH2/PolG2 axis enhances mitochondrial biogenesis via transcriptional regulation of Nrf2 and promotes chemotherapy resistance in acute myeloid leukaemia.

Xiuying Hu, Tianzhen Hu, Shuyun Cao, Li Jiang, Yan Zhou, Qin Fang, Jishi Wang

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

  1. Article
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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

7 authors.

Xiuying HuDepartment of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.ORCID http://orcid.org/0009-0009-0628-5805
Tianzhen HuDepartment of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.ORCID http://orcid.org/0009-0004-1757-5940
Shuyun CaoDepartment of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.ORCID http://orcid.org/0009-0007-9485-0477
Li JiangDepartment of Pharmacy, Daqin Cancer Hospital of Guizhou Province, Guizhou, China.ORCID http://orcid.org/0009-0008-7025-6796
Yan ZhouDepartment of Pediatric Nephrology and Rheumatology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.ORCID http://orcid.org/0009-0003-2071-4908
Qin FangDepartment of Pharmacy, Affiliated Hospital of Guizhou Medical University, Guizhou, China. fangqin@gmc.edu.cn.ORCID http://orcid.org/0000-0002-5414-7644
Jishi WangDepartment of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou, China. wangjishi9646@163.com.ORCID http://orcid.org/0000-0002-6338-3745

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although patients with acute myeloid leukaemia (AML) initially respond to conventional treatments, many patients die from AML progression and relapsed/refractory (RR) disease. Eradicating AML thus remains therapeutically challenging. In this study, we found a strong expression of aldehyde dehydrogenase 2 (ALDH2) and increased mitochondrial biosynthesis in samples from patients with drug-resistant AML, and these changes were strongly associated with poor prognosis and recurrence of AML. We examined the clonogenic capacity, growth and apoptosis of AML cells, as well as mitochondrial DNA expression and reactive oxygen species production. Our results revealed that chemotherapeutic agents triggered the activation of NF-E2-related factor 2 (Nrf2) and promoted high expression of ALDH2, mediating the compensatory activation of mitochondrial respiration and resistance to chemotherapeutic agents in RR AML cells. Nrf2 promoted mitochondrial respiration by activating ALDH2 expression and stabilising the expression of DNA polymerase-gamma2 (PolG2) in mitochondria. Inhibition of the Nrf2-ALDH2/PolG2 pathway reduced AML metabolic fitness and oxidative phosphorylation levels, highlighting the key role of this pathway in promoting cell survival. Nrf2 inhibition reduced the translation of ALDH2, induced a unique mitochondrial stress response and inhibited mitochondrial biosynthesis in AML cells. Importantly, tumours in an in vivo xenograft model were sensitive to combined Nrf2 and ALDH2 inhibition. Given the role of the Nrf2-ALDH2/PolG2 pathway in the progression of AML, inhibition of this pathway may prevent disease relapse/resistance and promote sensitisation to chemotherapy.

Indexed as

Aldehyde Dehydrogenase, MitochondrialDrug Resistance, NeoplasmLeukemia, Myeloid, AcuteMitochondriaNF-E2-Related Factor 2Organelle BiogenesisAnimalsApoptosisCell Line, TumorFemaleHumansMaleMiceReactive Oxygen SpeciesTranscription, GeneticAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanNFE2L2 protein, humanNF-E2-Related Factor 2Reactive Oxygen Species

Identifiers

PMID40796730
PMCPMC12344002

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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.