2. Academic Validation
  3. Targeting PRDX1 impairs acute myeloid leukemic blasts and stem cells by disrupting redox homeostasis

Targeting PRDX1 impairs acute myeloid leukemic blasts and stem cells by disrupting redox homeostasis

  • Cell Death Dis. 2025 Aug 18;16(1):627. doi: 10.1038/s41419-025-07831-6.
Zhenghao Li # 1,  Guangci Liu # 1,  Ziren Chen # 2,  Keming Li 1,  Zhe Yu 3,  Chao He 4,  Xinyu Ying 5,  Danling Huang 1,  Chengtian Tao 1,  Sajid Khan 1,  Yimeng Wang 1,  Fang-Lin Zhang 6,  Huan Li 1,  Yun Chen 7,  Jingfeng Zhou 1,  Li Yu 2,  Thomas J Kipps 8,  Yongxian Cheng 9,  Suping Zhang 10
Affiliations

Affiliations

  • 1 Shenzhen University International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Marshall Laboratory of Biomedical Engineering, Institute for Inheritance-Based Innovation of Chinese Medicine, Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, School of Basic Medical Sciences, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, PR China.
  • 2 Department of Hematology, Shenzhen University General Hospital, Shenzhen, Guangdong, PR China.
  • 3 Department of Hematology, Shandong Provincial Third Hospital, Shandong University, Shandong, PR China.
  • 4 Central Laboratory, Jiangsu University Affiliated Fourth Hospital, Zhenjiang, Jiangsu, PR China.
  • 5 Department of Clinical Laboratory, Ningbo Medical Centre Lihuili Hospital, Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, PR China.
  • 6 School of Chemistry, Chemistry Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, PR China.
  • 7 Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
  • 8 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
  • 9 Shenzhen University International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Marshall Laboratory of Biomedical Engineering, Institute for Inheritance-Based Innovation of Chinese Medicine, Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, School of Basic Medical Sciences, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, PR China. yxcheng@szu.edu.cn.
  • 10 Shenzhen University International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Marshall Laboratory of Biomedical Engineering, Institute for Inheritance-Based Innovation of Chinese Medicine, Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, School of Basic Medical Sciences, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, PR China. s9zhang@szu.edu.cn.
  • # Contributed equally.
PMID: 40825764 DOI: 10.1038/s41419-025-07831-6
Abstract

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis and limited therapeutic options. Leukemic stem cells (LSCs), which drive disease progression and confer resistance to therapy, pose a significant challenge to conventional treatment strategies. In this study, we identified and characterized the inhibitory mechanisms of TH37, a small molecule derived from traditional Chinese medicine, which selectively targets AML blasts and LSCs. Our analyses identified peroxiredoxin 1 (PRDX1), an enzyme that catalyzes the breakdown of hydrogen peroxide (a Reactive Oxygen Species), as the primary molecular target of TH37. We demonstrated that TH37 directly interacts with PRDX1, inhibiting its enzymatic activity and thereby elevating intracellular Reactive Oxygen Species levels in AML cells. PRDX1 was found to be overexpressed in AML, and its expression correlated with poor prognosis and the activation of AML- and cancer-associated pathways. Targeting PRDX1, either through lentiviral short-hairpin RNA-mediated silencing or TH37 treatment, induced Apoptosis, reduced colony formation, and impaired the engraftment and growth of AML cells in immunodeficient mouse models. Furthermore, TH37 synergized with conventional chemotherapeutic agent to significantly reduce the viability and colony-forming capacity of AML cells. These findings demonstrate the critical role of PRDX1 in AML pathogenesis and highlight its potential as a key therapeutic target to improve clinical outcomes for AML patients.

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