Evidence mapPaperPMID 40653487Full record

ArticleSignal transduction and targeted therapy2025

High mtDNA content identifies oxidative phosphorylation-driven acute myeloid leukemias and represents a therapeutic vulnerability.

Diego A Pereira-Martins, Isabel Weinhäuser, Emmanuel Griessinger, Juan L Coelho-Silva, Douglas R Silveira, Dominique Sternadt, Ayşegül Erdem, Bruno Kosa L Duarte, Prodromos Chatzikyriakou, Lynn Quek and 15 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

25 authors.

Diego A Pereira-MartinsDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.ORCID 0000-0002-3302-4311
Isabel WeinhäuserDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Emmanuel GriessingerDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Juan L Coelho-SilvaDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.
Douglas R SilveiraMyeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
Dominique SternadtDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Ayşegül ErdemDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Bruno Kosa L DuarteHematology and Transfusion Medicine Center, University of Campinas, Campinas, Brazil.
Prodromos ChatzikyriakouMyeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.ORCID 0000-0002-0048-4100
Lynn QuekMyeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
Antonio Bruno Alves-SilvaDepartment of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Fabiola TrainaDepartment of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.ORCID 0000-0003-4258-289X
Sara T Olalla SaadHematology and Transfusion Medicine Center, University of Campinas, Campinas, Brazil.
Jacobien R HilberinkDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Amanda Moreira-AguiarDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.
Maria L Salustiano-BandeiraDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.
Marinus M LimaDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.
Pedro L Franca-NetoDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.
Marcos A BezerraDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil.
Nisha K van der MeerDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Emanuele AmmatunaDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Eduardo M RegoDepartment of Medical Imaging, Haematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.ORCID 0000-0003-1567-4086
Gerwin HulsDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Jan Jacob SchuringaDepartment of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. j.j.schuringa@umcg.nl.
Antonio R Lucena-AraujoDepartment of Genetics, Federal University of Pernambuco, Recife, Brazil. antonio.araujo@ufpe.br.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic reprogramming is a hallmark of cancer, with acute myeloid leukemia (AML) being no exception. Mitochondrial function, particularly its role in protecting tumor cells against chemotherapy, is of significant interest in AML chemoresistance. In this study, we identified mitochondrial DNA content (mtDNAc), measured by quantitative PCR, as a simple and precise marker to stratify the metabolic states of AML patients. We show that patients with high mtDNAc are associated with increased mitochondrial metabolism and a higher dependency on oxidative phosphorylation (OXPHOS), often correlating with chemoresistance. Clinically, patients receiving cytarabine and an anthracycline-based regimen (7 + 3 regimen) experienced inferior relapse-free survival and a higher overall rate of leukemia recurrence. Ex vivo experiments using primary AML samples confirmed cytarabine resistance in high mtDNAc patients, which could be overcome by inhibiting mitochondrial complex I. The FDA-approved drug metformin, which targets mitochondrial metabolism, significantly enhanced apoptosis in response to chemotherapy or targeted agents, such as venetoclax, in AML models. However, metformin-treated cells adapted by increasing glycolysis and NAD

Indexed as

DNA, MitochondrialLeukemia, Myeloid, AcuteOxidative PhosphorylationAdultAgedBridged Bicyclo Compounds, HeterocyclicCytarabineDrug Resistance, NeoplasmFemaleHumansMaleMetforminMiddle AgedMitochondriaSulfonamidesBridged Bicyclo Compounds, HeterocyclicCytarabineDNA, MitochondrialMetforminSulfonamidesvenetoclax

Identifiers

PMID40653487
PMCPMC12256626

What Socratic holds

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Registered trials

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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.