Evidence map›Paper›PMID 41392978›Full record

ArticleThe Journal of clinical investigation2025

Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche.

Hao Gu, Lietao Weng, Chiqi Chen, Xiaoxin Hao, Rongkun Tao, Xin Qi, Xiaoyun Lai, Ligen Liu, Tinghua Zhang, Yiming Jiang and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 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. Article
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

23 authors.

Hao GuKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medicine, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China.
Lietao WengInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chiqi ChenInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoxin HaoInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Rongkun TaoClinical Research Institute, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Fujian, China.
Xin QiDepartment of Anesthesiology, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoyun LaiInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ligen LiuInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tinghua ZhangInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yiming JiangDepartment of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jin WangSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Wei-Guang LiDepartment of Rehabilitation Medicine, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, and Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Zhuo YuInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Li XieInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yaping ZhangInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoxiao HeInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ye YuSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Yi YangOptogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering and.
Dehua WuDepartment of Anesthesiology, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuzheng ZhaoOptogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering and.
Tian-Le XuDepartment of Anesthesiology, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Guo-Qiang ChenKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medicine, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China.
Junke ZhengInstitute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The metabolic microenvironment plays important roles in tumorigenesis, but how leukemia-initiating cells (LICs) response to the acidic BM niche remains largely unknown. Here, we show that acid-sensing ion channel 3 (ASIC3) dramatically delays leukemogenesis. Asic3 deletion results in a remarkably enhanced self-renewal, reduced differentiation, and 9-fold greater number of murine acute myeloid LICs. We developed an ultrasensitive, ratiometric, genetically encoded fluorescent pH sensor (pHluorin3) and demonstrated that LICs prefer localizing in the endosteal niche with a neutral pH range of 7.34-7.42, but not in the vascular niche with a lower pH range of 6.89-7.22. Unexpectedly, acid-ASIC3 signaling inhibits both murine and human LIC activities in a noncanonical manner by interacting with the N-terminal of STIM1 to reduce calcium-mediated CAMK1-CREB-MEIS1-LDHA levels, without inducing cation currents. This study reveals a pathway in suppression of leukemogenesis in the acidic BM niche and provides insight into targeting LICs or other cancer stem cells through pH-dependent ASICs.

Indexed as

Acid Sensing Ion ChannelsBone MarrowLeukemia, Myeloid, AcuteNeoplastic Stem CellsStem Cell NicheAnimalsCarcinogenesisHumansHydrogen-Ion ConcentrationMiceMice, KnockoutNeoplasm ProteinsStromal Interaction Molecule 1Tumor MicroenvironmentAcid Sensing Ion ChannelsNeoplasm ProteinsStim1 protein, mouseStromal Interaction Molecule 1HematologyLeukemiasMetabolismOncologyStem Cells

Identifiers

PMID41392978
PMCPMC12700551

What OpenQuestion holds

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Registered trials

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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.