Evidence map›Paper›PMID 41275169›Full record

ArticleBMC cancer2025

ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.

Lei Zhao, Xinrong Xiang, Ailing Zhong, Hongbin Yu, Jinjun Yang, Mengran Chen, Hong Ding, Chenlu Yang, Yu Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2025. 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

9 authors.

Lei Zhao *Department of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China.ORCID http://orcid.org/0009-0000-3203-4588
Xinrong Xiang *Department of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China.
Ailing ZhongState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Hongbin YuDepartment of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China.
Jinjun YangDepartment of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China.
Mengran ChenDepartment of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China.
Hong DingDepartment of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China.
Chenlu YangDepartment of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China. yangchenlu@wchscu.cn.
Yu WuDepartment of Hematology and Institute of Hematology, West China Hospital, Sichuan University, #37 Guo Xue Xiang Street, Chengdu, 610041, PR China. wu_yu@scu.edu.cn.ORCID http://orcid.org/0000-0001-8708-9711

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVenetoclax (VEN) in combination with hypomethylating agents has emerged as a pivotal therapy for elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, monocytic AML exhibit greater resistance to VEN-based regimens compared to non-monocytic AML. Identifying exploitable vulnerabilities will mitigate resistance and relapse.

methodsWe conducted a comprehensive analysis of VEN resistance mechanisms in monocytic AML by integrating bulk AML datasets, single-cell RNA sequencing (scRNA-seq) of AML patient bone marrow and patient-derived xenograft (PDX) models, as well as lipidomic sequencing of induced VEN-resistant cell lines. Additionally, we examined the monocytic markers in VEN-resistant cell lines and assessed VEN sensitivity after knocking down the key sphingolipid metabolism gene ASAH1.

resultsAnalysis of bulk RNA-seq data revealed elevated expression of sphingolipid metabolism genes in the French-American-British (FAB) M5 subtype, which exhibited poor response to VEN-based treatment. Further analysis of scRNA-seq data showed that monocytic AML cells surviving VEN treatment demonstrated the highest sphingolipid metabolism score, particularly in CD14⁺ITGAX⁺ monocytic AML cells. Notably, induced VEN-resistant cell lines exhibited significantly increased monocytic markers and differential sphingolipid metabolism profiles compared to parental cells. Among the key regulators of sphingolipid metabolism, ASAH1 was upregulated, while SPHK1 was downregulated. Knocking down ASAH1 enhanced VEN sensitivity without reducing the expression of monocytic markers CD14/CD64.

conclusionsThese findings suggest that aberrant sphingolipid metabolism contribute to AML resistance to VEN.

Indexed as

Acid CeramidaseBridged Bicyclo Compounds, HeterocyclicDrug Resistance, NeoplasmLeukemia, Myeloid, AcuteSphingolipidsSulfonamidesAnimalsAntineoplastic AgentsCell Line, TumorHumansMiceMonocytesPhenotypeXenograft Model Antitumor AssaysAcid CeramidaseAntineoplastic AgentsASAH1 protein, humanBridged Bicyclo Compounds, HeterocyclicSphingolipidsSulfonamidesvenetoclaxAcute myeloid leukemiaDrug resistanceMonocyticSphingolipidVenetoclax

Identifiers

PMID41275169
PMCPMC12781537

What Socratic holds

Textmetadata
LicenceCC BY
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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.