机构：[1]State Key Laboratory of Systems Medicine for Cancer, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.[2]Department of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[3]Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[4]Shanghai Cancer Institute, Shanghai, China.[5]Animal Facility of Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[6]Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.[7]Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha, China.[8]Clinical Laboratory Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[9]Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[10]Department of Hematology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[11]Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[12]School of Biomedical Engineering, ShanghaiTech University, Shanghai, China.
The spleen plays a critical role in the pathogenesis of leukemia. However, our understanding of the splenic niche is very limited. Herein, we report that induced expression of the secreted protein Gremlin 1 in a mouse model restrains chronic myeloid leukemia (CML) progression and synergizes with tyrosine kinase inhibitor treatment, whereas blockade of Gremlin 1 promotes CML development. Intriguingly, the effect of Gremlin 1 is most evident in the spleen but not in the bone marrow. Gremlin 1 induces apoptosis of leukemic stem cells via antagonizing the BMP pathway. Single-cell RNA sequencing and experimental validation together show that Gremlin 1 marks a unique stromal cell population in the spleens of both mice and humans. Genetic ablation of Gremlin 1+ cells leads to accelerated CML progression. Collectively, Gremlin 1 and Gremlin 1+ cells are key defensive niche components in the spleen that limit CML progression, revealing an unprecedented mechanism for the body to fight off leukemia.
基金：
National Natural Science Foundation of China [U23A20454, NSFC82372873, NSFC82200170]; Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University [21TQ1400225]; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20181706]; Shanghai Science and Technology Commission [20JC1410100]; Innovative research team of high-level local universities in Shanghai, 111 project [B21024]; Central University Outstanding Youth Team Cultivation Program
第一作者机构：[1]State Key Laboratory of Systems Medicine for Cancer, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
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通讯作者：
推荐引用方式(GB/T 7714)：
Wang Jinming,Xu Penghui,Ji Zhongzhong,et al.A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway[J].NATURE CANCER.2025,6(4):doi:10.1038/s43018-025-00933-2.
APA：
Wang, Jinming,Xu, Penghui,Ji, Zhongzhong,Cheng, Chaping,Liu, Yiyun...&Zhu, Helen He.(2025).A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.NATURE CANCER,6,(4)
MLA：
Wang, Jinming,et al."A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway".NATURE CANCER 6..4(2025)
医学