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journal article·2026-05-10Open access

PIEZO1 is Required for Acute Myeloid Leukemia Progression and Leukemia Stem Cell Maintenance via HIF1A‐SLC7A11 Axis‐Mediated Ferroptosis Defense

Tiantian Zhang, Ziyan Cao, Kexin Gao, Shuxin Yao, Yanbing Zheng, Manman Cui, Rong Yin, Guoqiang Han, Jin Hu, Chengyi Wang, Haojian Zhang

Advanced Science
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Abstract

ABSTRACT Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy that arises from leukemia stem cells (LSCs) transformed from normal hematopoietic stem progenitor cells (HSPCs). Compared to normal HSPCs, LSCs acquire various adaptive properties that enable their survival and regenerative capacity under environmental challenges. However, the key regulators underlying these adaptative features in AML LSCs remain largely unknown. Here, the mechanosensor PIEZO1 as a key factor in promoting acute myeloid leukemia progression and maintaining LSC stemness by HIF1A‐SLC7A11 axis‐mediated ferroptosis defense is uncovered. PIEZO1 deletion impairs cystine uptake and induces ROS and lipid peroxidation, causing ferroptosis of leukemia cells. Mechanistically, HIF1A mediates the function of PIEZO1 by transcriptionally regulating the expression of SLC7A11 and SLC3A2. Further, inhibition of PIEZO1 and SLC7A11 suppresses LSC function and contributes to AML treatment. In summary, this findings reveal that LSCs control cystine uptake through the PIEZO1‐HIF1A‐SLC7A11 axis to defend against ferroptosis, representing a unique vulnerability of LSCs.
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Research context

OpenAlex topics: Erythrocyte Function and Pathophysiology · Ferroptosis and cancer prognosis · Cancer Cells and Metastasis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Hubei Key Laboratory of Stomatology Key Laboratory of Oral Biomedicine Ministry of Education School & Hospital of Stomatology Wuhan University Wuhan China

Frontier Science Center For Immunology and Metabolism Medical Research Institute Wuhan University Wuhan China

Department of Hematology Zhongnan Hospital Wuhan University Wuhan China

Department of Pediatrics Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center) College of Clinical Medicine For Obstetrics & Gynecology and Pediatrics Fujian Medical University Fuzhou China

Taikang Center for Life and Medical Sciences Wuhan University Wuhan China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · Natural Science Foundation of Fujian Province · Fundamental Research Funds for the Central Universities

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