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Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma.
Zhu, Yinghong; Jian, Xingxing; Chen, Shuping; An, Gang; Jiang, Duanfeng; Yang, Qin; Zhang, Jingyu; Hu, Jian; Qiu, Yi; Feng, Xiangling; Guo, Jiaojiao; Chen, Xun; Li, Zhengjiang; Zhou, Ruiqi; Hu, Cong; He, Nihan; Shi, Fangming; Huang, Siqing; Liu, Hong; Li, Xin; Xie, Lu; Zhu, Yan; Zhao, Lia; Jiang, Yichuan; Li, Jian; Wang, Jinuo; Qiu, Lugui; Chen, Xiang; Jia, Wei; He, Yanjuan; Zhou, Wen.
  • Zhu Y; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Jian X; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Chen S; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • An G; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
  • Jiang D; Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Yang Q; Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Zhang J; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Hu J; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Qiu Y; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Feng X; Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
  • Guo J; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Chen X; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Li Z; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Zhou R; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Hu C; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • He N; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Shi F; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Huang S; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Liu H; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Li X; Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Xie L; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Zhu Y; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Zhao L; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Jiang Y; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Li J; Peking Union Medical College Hospital, Chinese Academy Medical Society & Peking Union Medical College, Beijing, China.
  • Wang J; Peking Union Medical College Hospital, Chinese Academy Medical Society & Peking Union Medical College, Beijing, China.
  • Qiu L; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
  • Chen X; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: chenxiangck@126.com.
  • Jia W; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address: weijia1@hkbu.edu.hk.
  • He Y; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
  • Zhou W; Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of
Cell Metab ; 36(1): 159-175.e8, 2024 01 02.
Article en En | MEDLINE | ID: mdl-38113887
ABSTRACT
The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Microbioma Gastrointestinal / Mieloma Múltiple Límite: Humans Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Microbioma Gastrointestinal / Mieloma Múltiple Límite: Humans Idioma: En Año: 2024 Tipo del documento: Article