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已发表论文
LRG1 通过破坏髓系祖细胞的调控促进急性髓系白血病进展
Authors Guo R, Wu P, Yao S, Liu F
Received 28 July 2025
Accepted for publication 11 November 2025
Published 17 December 2025 Volume 2025:15 Pages 235—246
DOI https://doi.org/10.2147/BLCTT.S556618
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Wilson Gonsalves
Rongxia Guo,1,* Peng Wu,2,* Shuxin Yao,3 Fumei Liu1
1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Frontier Science Center for Immunology and Metabolism, School of Medicine, Medical Research Institute, Wuhan University, Wuhan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Rongxia Guo, Email guorongxia2015@163.com
Background: Acute myeloid leukemia (AML) remains clinically challenging due to its molecular heterogeneity and poor outcomes, highlighting the urgent need for novel biomarkers and therapeutic targets.
Purpose: This study aims to identify and characterize the role of leucine-rich α-2-glycoprotein 1 (LRG1) in AML, evaluating its potential as both a prognostic biomarker and a therapeutic target.
Methods: We conducted an integrated basic and clinical investigation of LRG1 in AML. Methods included analysis of LRG1 expression in patient samples versus controls and pre- versus post-treatment, assessment of its clinical correlations with mutations and subtypes, and evaluation of its prognostic impact. Functional validation was performed using LRG1 knockdown models to assess effects on colony formation, apoptosis, and differentiation. Single-cell RNA profiling was utilized to identify LRG1-enriched cell populations and explore its role in microenvironmental crosstalk.
Results: Integrated analysis revealed significantly elevated LRG1 expression in AML patients compared to controls (P< 0.001), with levels decreasing post-treatment (P< 0.001). High LRG1 expression correlated with FLT3 mutations (P< 0.01), M3-M5 AML subtypes (M0&M1&M2 VS M3, P< 0.001; M0&M1&M2 VS M4, P< 0.01; M0&M1&M2 VS M5, P< 0.001; M3 VS M5, P< 0.05; M4 VS M5, P< 0.05), and worse survival (P< 0.01). Functionally, LRG1 knockdown impaired colony formation (P< 0.001), increased apoptosis (P< 0.001), and disrupted differentiation (P< 0.01). Single-cell profiling identified LRG1 enrichment in hematopoietic stem and progenitor cells (HSPCs) and myeloid progenitors, where it facilitated microenvironmental crosstalk via Macrophage Migration Inhibitory Factor (MIF), Galactoside-binding lectin (GALECTIN), and Cyclophilin A (CypA) signals.
Conclusion: Our findings establish LRG1 as a robust prognostic biomarker and a key functional regulator of AML maintenance through myeloid progenitor dysregulation, presenting it as a promising target for new therapeutic strategies.
Keywords: AML, hematopoietic dysregulation, LRG1, microenvironmental crosstalk
1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Frontier Science Center for Immunology and Metabolism, School of Medicine, Medical Research Institute, Wuhan University, Wuhan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Rongxia Guo, Email guorongxia2015@163.com
Background: Acute myeloid leukemia (AML) remains clinically challenging due to its molecular heterogeneity and poor outcomes, highlighting the urgent need for novel biomarkers and therapeutic targets.
Purpose: This study aims to identify and characterize the role of leucine-rich α-2-glycoprotein 1 (LRG1) in AML, evaluating its potential as both a prognostic biomarker and a therapeutic target.
Methods: We conducted an integrated basic and clinical investigation of LRG1 in AML. Methods included analysis of LRG1 expression in patient samples versus controls and pre- versus post-treatment, assessment of its clinical correlations with mutations and subtypes, and evaluation of its prognostic impact. Functional validation was performed using LRG1 knockdown models to assess effects on colony formation, apoptosis, and differentiation. Single-cell RNA profiling was utilized to identify LRG1-enriched cell populations and explore its role in microenvironmental crosstalk.
Results: Integrated analysis revealed significantly elevated LRG1 expression in AML patients compared to controls (P< 0.001), with levels decreasing post-treatment (P< 0.001). High LRG1 expression correlated with FLT3 mutations (P< 0.01), M3-M5 AML subtypes (M0&M1&M2 VS M3, P< 0.001; M0&M1&M2 VS M4, P< 0.01; M0&M1&M2 VS M5, P< 0.001; M3 VS M5, P< 0.05; M4 VS M5, P< 0.05), and worse survival (P< 0.01). Functionally, LRG1 knockdown impaired colony formation (P< 0.001), increased apoptosis (P< 0.001), and disrupted differentiation (P< 0.01). Single-cell profiling identified LRG1 enrichment in hematopoietic stem and progenitor cells (HSPCs) and myeloid progenitors, where it facilitated microenvironmental crosstalk via Macrophage Migration Inhibitory Factor (MIF), Galactoside-binding lectin (GALECTIN), and Cyclophilin A (CypA) signals.
Conclusion: Our findings establish LRG1 as a robust prognostic biomarker and a key functional regulator of AML maintenance through myeloid progenitor dysregulation, presenting it as a promising target for new therapeutic strategies.
Keywords: AML, hematopoietic dysregulation, LRG1, microenvironmental crosstalk