Evidence map›Paper›PMID 41998301›Full record

ArticleLeukemia2026

PRMT5 inhibition sensitizes B-cell lymphoma cells to ferroptosis.

Yunxia Liu, Ruoyu Chen, Xiaoyue Gao, Fen Zhu, Qinyu Ni, Paul D Bates, Sunny Wu, Zhuoyan Zai, Victoria A Obernberger, Kavinu Weerawardhene and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 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. 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

15 authors.

Yunxia LiuDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Ruoyu ChenDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Xiaoyue GaoDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Fen ZhuDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Qinyu NiDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.ORCID http://orcid.org/0009-0004-3220-1955
Paul D BatesCarbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Sunny WuDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Zhuoyan ZaiDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Victoria A ObernbergerDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Kavinu WeerawardheneDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Taylor K TourdotDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Sophie PettaDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Madison J ConyersDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Christian M CapitiniCarbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.ORCID http://orcid.org/0000-0002-2276-6731
Lixin RuiDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. lrui@medicine.wisc.edu.ORCID http://orcid.org/0000-0002-5762-8937

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Justine Yang Bruce · 1985 to 2026
$142.6M
Targeting EGR1 signaling pathways in diffuse large B cell lymphomaR01CA266354 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Lixin Rui · 2022 to 2026
$1.7M
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA266354
6 · The paper itself

Abstract

Protein arginine methyltransferase 5 (PRMT5) is overexpressed in B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). While PRMT5 is known to regulate multiple oncogenic pathways, including PI3K-AKT signaling, its role in lipid metabolism and ferroptosis, a regulated, iron-dependent cell death driven by lipid peroxidation, remains poorly understood. Here, we identify a novel role for PRMT5 in suppressing ferroptosis in DLBCL and MCL cells through upregulation of SLC7A11, which imports cystine for glutathione (GSH) biosynthesis. This effect is mediated by the AKT-MYC-ATF5 signaling axis. ATF5, a MYC-regulated transcription factor overexpressed in these lymphomas, induces SLC7A11 expression. In addition, ATF5 promotes the expression of ATF4, another key regulator of the ferroptotic response, which forms heterodimers with ATF5 to further reinforce this regulatory network. PRMT5 inhibition sensitizes lymphoma cells to ferroptosis inducers such as dimethyl fumarate (DMF), an electrophile that irreversibly depletes GSH via succination. Notably, combined treatment with the PRMT5 inhibitor GSK3326595 and DMF synergistically enhances anti-tumor activity in a patient-derived xenograft (PDX) model. These findings reveal a previously unrecognized PRMT5-ATF5-SLC7A11 axis that drives ferroptosis resistance in B-cell lymphomas and provide a strong rationale for targeting PRMT5 to potentiate ferroptosis-based therapies in relapsed or refractory disease.

Indexed as

FerroptosisLymphoma, B-CellLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-CellProtein-Arginine N-MethyltransferasesActivating Transcription FactorsAmino Acid Transport System y+AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceSignal TransductionXenograft Model Antitumor AssaysActivating Transcription FactorsAmino Acid Transport System y+ATF5 protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesSLC7A11 protein, human

Identifiers

PMID41998301
PMCPMC13233303

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.