Evidence mapPaperPMID 41730833Full record

ArticleCell death & disease2026

Marrow leptin-LEPR signaling rewires mitochondrial oxidative metabolism to confer chemoresistance in acute myeloid leukemia.

Xinai Liao, Wei Dai, Xiaolin Xu, Danni Cai, Maoqing Tan, Zukai Wang, Yanrong Huang, Diyu Hou, Jingru Liu, Liuhuan Wang and 5 more

Abstract read
In one paragraph

Article in Cell death & disease, 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.

Xinai Liao *Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0009-0003-5886-336X
Wei Dai *Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
Xiaolin XuCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0009-0005-2345-7454
Danni CaiCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0000-0001-9254-1207
Maoqing TanCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0000-0002-6185-9439
Zukai WangDepartment of Colorectal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350005, China.ORCID http://orcid.org/0000-0001-5274-6531
Yanrong HuangCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0009-0003-3652-6741
Diyu HouCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0009-0009-8561-7424
Jingru LiuCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0000-0001-5626-1216
Liuhuan WangCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0009-0001-9122-4143
Jin WangCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
Xiaoting WangCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0000-0003-1031-6968
Shuxia ZhangFujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.ORCID http://orcid.org/0000-0002-0649-5556
Xinjian LinKey Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, Fujian, 350122, China. xlin@fjmu.edu.cn.ORCID http://orcid.org/0009-0009-4583-8118
Huifang HuangCentral Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China. huanghuif@fjmu.edu.cn.ORCID http://orcid.org/0000-0002-8548-028X

Funding

China Postdoctoral Science Foundation 2024M760463National Natural Science Foundation of China (National Science Foundation of China) 82400199
6 · The paper itself

Abstract

Leptin is abundant within marrow adipose tissue, yet its impact on acute myeloid leukemia (AML) therapy response is undefined. Here, we report that elevated bone-marrow leptin and blast-cell leptin-receptor (LEPR) levels strongly associate with poor cytarabine (Ara-C) clearance and reduced survival in newly diagnosed AML patients. Mechanistic and functional validation in human AML lines, primary blasts, and two syngeneic mouse models (MLL-AF9, AML1-ETO9a) shows that exogenous leptin markedly blunts Ara-C cytotoxicity, whereas the high-affinity LEPR antagonist Allo-aca restores chemosensitivity without altering baseline leukemia growth. Leptin up-regulates LEPR and triggers JAK2/STAT3 signaling that boosts mitochondrial complex Ⅰ activity, oxidative phosphorylation, and mitochondrial reactive oxygen species (mtROS); the resulting mtROS surge activates a compensatory antioxidant program that shields blasts from drug-induced oxidative damage. These data identify an adipokine-driven metabolic circuit governing AML chemoresistance and reveal LEPR blockade as a tractable strategy to improve outcomes, underscoring adipose-tumor crosstalk as a general therapeutic vulnerability.

Indexed as

Bone MarrowDrug Resistance, NeoplasmLeptinLeukemia, Myeloid, AcuteMitochondriaReceptors, LeptinAnimalsCell Line, TumorCytarabineFemaleHumansMiceOxidative PhosphorylationReactive Oxygen SpeciesSignal TransductionSTAT3 Transcription FactorCytarabineLEPR protein, humanLeptinReactive Oxygen SpeciesReceptors, LeptinSTAT3 Transcription Factor

Identifiers

PMID41730833
PMCPMC12966444

What Socratic 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 Socratic graph.