Evidence map›Paper›PMID 42538429›Full record

ArticleLeukemia2026

Targeting ACSF2 overcomes Ara-C resistance in acute myeloid leukemia via the cholesterol metabolism-ERK signaling axis.

Chenxi Liao, Jin Wen, Xiao Ma, Nan Wang, Ying Chen, Lei Li, Lingbo Liu, Danyue Peng

Abstract read
PubMed 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

8 authors.

Chenxi Liao *Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0003-4423-8750
Jin Wen *Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.ORCID http://orcid.org/0000-0002-3140-2999
Xiao MaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0003-3221-4188
Nan WangInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0009-0005-4293-296X
Ying ChenInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0003-4579-7896
Lei LiDepartment of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0003-1404-0321
Lingbo LiuInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. liulingbo@hust.edu.cn.ORCID http://orcid.org/0000-0002-3556-459X
Danyue PengInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2018XH0216@hust.edu.cn.ORCID http://orcid.org/0009-0009-3385-6140

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81370660National Natural Science Foundation of China (National Science Foundation of China) 81973999National Natural Science Foundation of China (National Science Foundation of China) 82270184
6 · The paper itself

Abstract

Therapeutic resistance to cytarabine (Ara-C), a cornerstone of acute myeloid leukemia (AML) therapy, remains an unmet clinical need. Here, we identify ACSF2 as a key metabolic determinant of Ara-C resistance. ACSF2 inhibition suppresses Ara-C-resistant AML cell proliferation, restores Ara-C sensitivity in vitro and in vivo. Mechanistically, ACSF2 inhibition impairs cholesterol esterification. Therefore, the increased cholesterol accumulation on mitochondrial membranes results in mitochondrial dysfunction, elevated mitochondrial reactive oxygen species (ROS), and suppression of pro-survival ERK signaling. Furthermore, we first established SREBF1 as a direct transcriptional activator of ACSF2 in this context. Notably, the SREBF1 inhibitor fatostatin synergizes with Ara-C against resistant AML with downregulation of ACSF2. These findings define a crucial role of ACSF2 in Ara-C resistance and highlight the SREBF1-ACSF2 axis as a promising therapeutic target for relapsed/refractory AML.

Indexed as

CholesterolCytarabineDrug Resistance, NeoplasmLeukemia, Myeloid, AcuteMAP Kinase Signaling SystemAnimalsAntimetabolites, AntineoplasticCell Line, TumorCell ProliferationHumansMicePyridinesReactive Oxygen SpeciesSterol Regulatory Element Binding Protein 1ThiazolesXenograft Model Antitumor AssaysAntimetabolites, AntineoplasticCholesterolCytarabinefatostatinPyridinesReactive Oxygen SpeciesSREBF1 protein, humanSterol Regulatory Element Binding Protein 1Thiazoles

Identifiers

PMID42538429

What OpenQuestion holds

Textmetadata
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.