Evidence map›Paper›PMID 41559050›Full record

ArticleNature communications2026

TET1 as a master regulator controlling GPX4-dependent and -independent ferroptosis surveillance in acute myeloid leukemia.

Lingling Yang, Jun Lu, Weina Yun, Xinquan Yang, Jie Sun, Chaodong Ge, Fei Han, Xiang Li, Junxia Min, He Huang and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Lingling Yang *Department of Pharmacology, Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Jun Lu *Department of Pharmacology, Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Weina Yun *Department of Pharmacology, Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Xinquan YangThe First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Jie SunBone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Chaodong GeThe Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China.
Fei HanDepartment of Pharmacology, Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Xiang LiDepartment of Pharmacology, Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Junxia MinThe First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0001-8099-6327
He HuangBone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Fudi WangThe Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China. fwang@zju.edu.cn.ORCID http://orcid.org/0000-0001-8730-0003
Xi JiangDepartment of Pharmacology, Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China. xjiang@hznu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32270615National Natural Science Foundation of China (National Science Foundation of China) 81970144
6 · The paper itself

Abstract

Ferroptosis, an iron-dependent, lipid peroxidation-driven programmed cell death, holds substantial promise for cancer therapy, yet its translational potential is hindered by widespread intrinsic resistance. While glutathione peroxidase 4 (GPX4) is a well-established ferroptosis suppressor, the epigenetic circuitry coordinating GPX4-related mechanisms remains elusive. Here, via genome-wide screening, we identify ten-eleven translocation 1 (TET1)-a key mediator of DNA 5-hydroxymethylation-as a master controller of cancer cell ferroptosis susceptibility. In acute myeloid leukemia (AML), TET1 enhances 5hmC deposition at the glutamate-cysteine ligase catalytic subunit (GCLC) promoter to activate glutathione/γ-glutamyl-peptide metabolism, fortifying GPX4-dependent defense. Concurrently, TET1 activates NFκB signaling to upregulate GTP cyclohydrolase-1 (GCH1), conferring GPX4-independent ferroptosis resistance. Critically, co-targeting TET1/GCLC/GCH1 with low-dose ferroptosis inducers exhibits potent therapeutic effects against both ferroptosis-sensitive and -resistant AML. Our work positions TET1 as a pivotal epigenetic hub governing ferroptosis surveillance, and provides a translatable strategy to overcome ferroptosis resistance in cancer, with AML as a paradigm.

Indexed as

FerroptosisLeukemia, Myeloid, AcuteMixed Function OxygenasesPhospholipid Hydroperoxide Glutathione PeroxidaseProto-Oncogene ProteinsAnimalsCell Line, TumorDNA MethylationEpigenesis, GeneticGTP CyclohydrolaseHumansMiceNF-kappa BGTP CyclohydrolaseMixed Function OxygenasesNF-kappa BPhospholipid Hydroperoxide Glutathione PeroxidaseProto-Oncogene ProteinsTET1 protein, human

Identifiers

PMID41559050
PMCPMC12917170

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.