Evidence map›Paper›PMID 41237364›Full record

ArticleBlood2026

Glutaredoxin 2 is essential for AML survival through mitochondrial permeability transition pore regulation.

Tianyi Ling, Cristiana O'Brien, Jonathan R St-Germain, Vincent Rondeau, Mary Shi, Jacob M Berman, Adrianna Cepa, Paula Saez Raez, Mark Wunderlich, Katharine M Carter and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Tianyi LingPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0009-0007-4410-3043
Cristiana O'BrienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Jonathan R St-GermainPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Vincent RondeauPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Mary ShiPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0009-0007-2311-7622
Jacob M BermanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-6454-4996
Adrianna CepaDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Paula Saez RaezDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.ORCID 0000-0002-7030-9439
Mark WunderlichDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.ORCID 0000-0002-2166-5146
Katharine M CarterDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.ORCID 0000-0002-6332-1886
Cody StillwellDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Christina SextonDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.ORCID 0009-0008-8423-4619
Rachel Culp-HillDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO.ORCID 0000-0003-3000-083X
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO.ORCID 0000-0002-7296-4963
Saeer A AdeelPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Andy G X ZengPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Suraj BansalPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0003-4023-6635
Emily TsaoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
He Tian ChenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-8233-7448
John E DickDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-9527-8317
Mark D MindenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-9089-8816
Andrea ArrudaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Maria L AmayaDivision of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.ORCID 0000-0001-9503-5019
Anastasia N TikhonovaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-6712-1606
Kristin J HopePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO.ORCID 0000-0002-2258-6490
Brian RaughtPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-6145-4776
Courtney L JonesPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0003-0672-1493

Funding

Therapeutic insights through patient derived leukemia xenograftsR50CA211404 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Mark Wunderlich · 2016 to 2026
$1.9M
Targeting Polyamine Metabolism in Relapsed Acute Myeloid Leukemia Stem CellsR37CA291896 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Courtney Lynn Jones · 2025 to 2026
$1.1M
NCI NIH HHS R37 CA291896NCI NIH HHS R50 CA211404
6 · The paper itself

Abstract

abstractPatients with acute myeloid leukemia (AML) have a poor 5-year survival rate, highlighting the need for the identification of new approaches to target this disease. AML is highly dependent on glutathione (GSH) metabolism for survival. Although the metabolic role of GSH is well characterized in AML, the contribution of protein glutathionylation, a reversible modification that protects protein thiols from oxidative damage, remains largely unexplored. Therefore, we sought to elucidate the role of protein glutathionylation in AML pathogenesis. Here, we demonstrate that protein glutathionylation is essential for AML cell survival. Specifically, the loss of glutaredoxin 2 (GLRX2), an enzyme that removes GSH modifications, resulted in selective primary AML cell death while sparing normal human hematopoietic stem and progenitor cells. Unbiased proteomic analysis revealed increased mitochondrial protein glutathionylation upon GLRX2 depletion, accompanied by mitochondrial dysfunction, including impaired oxidative phosphorylation, reduced mitochondrial membrane potential, and increased opening of the mitochondrial permeability transition pore (mPTP). Further investigation identified adenosine triphosphate synthase subunit O (ATP5PO), a key regulator of mPTP opening and a component of the ATP synthase complex, as a critical GLRX2 target. Disruption of ATP5PO glutathionylation partially restored mPTP function and rescued AML cell viability after GLRX2 depletion. Moreover, both genetic and pharmacological inhibition of mPTP opening restored the leukemic potential of primary AML specimens in the absence of GLRX2. By disrupting glutathionylation-dependent mitochondrial homeostasis, this study reveals a novel vulnerability in AML that could inform future therapeutic strategies.

Indexed as

GlutaredoxinsLeukemia, Myeloid, AcuteMitochondrial Membrane Transport ProteinsCell SurvivalGlutathioneHumansMitochondriaMitochondrial Permeability Transition PoreMitochondrial Proton-Translocating ATPasesOxidative PhosphorylationGLRX2 protein, humanGlutaredoxinsGlutathioneMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMitochondrial Proton-Translocating ATPases

Identifiers

PMID41237364
PMCPMC12917306

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.