Nature Communications (Apr 2023)
Excessive serine from the bone marrow microenvironment impairs megakaryopoiesis and thrombopoiesis in Multiple Myeloma
- Chunmei Kuang,
- Meijuan Xia,
- Gang An,
- CuiCui Liu,
- Cong Hu,
- Jingyu Zhang,
- Zhenhao Liu,
- Bin Meng,
- Pei Su,
- Jiliang Xia,
- Jiaojiao Guo,
- Yinghong Zhu,
- Xing Liu,
- Xuan Wu,
- Yi Shen,
- Xiangling Feng,
- Yanjuan He,
- Jian Li,
- Lugui Qiu,
- Jiaxi Zhou,
- Wen Zhou
Affiliations
- Chunmei Kuang
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Meijuan Xia
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- Gang An
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- CuiCui Liu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- Cong Hu
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Jingyu Zhang
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Zhenhao Liu
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Bin Meng
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Pei Su
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- Jiliang Xia
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Jiaojiao Guo
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Yinghong Zhu
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Xing Liu
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Xuan Wu
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Yi Shen
- Department of Orthopaedic Surgery, Second Xiangya Hospital, Central South University
- Xiangling Feng
- Xiangya School of Public Health, Central South University
- Yanjuan He
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- Jian Li
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Lugui Qiu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- Jiaxi Zhou
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
- Wen Zhou
- Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University
- DOI
- https://doi.org/10.1038/s41467-023-37699-z
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
Abstract Thrombocytopenia is a major complication in a subset of patients with multiple myeloma (MM). However, little is known about its development and significance during MM. Here, we show thrombocytopenia is linked to poor prognosis in MM. In addition, we identify serine, which is released from MM cells into the bone marrow microenvironment, as a key metabolic factor that suppresses megakaryopoiesis and thrombopoiesis. The impact of excessive serine on thrombocytopenia is mainly mediated through the suppression of megakaryocyte (MK) differentiation. Extrinsic serine is transported into MKs through SLC38A1 and downregulates SVIL via SAM-mediated tri-methylation of H3K9, ultimately leading to the impairment of megakaryopoiesis. Inhibition of serine utilization or treatment with TPO enhances megakaryopoiesis and thrombopoiesis and suppresses MM progression. Together, we identify serine as a key metabolic regulator of thrombocytopenia, unveil molecular mechanisms governing MM progression, and provide potential therapeutic strategies for treating MM patients by targeting thrombocytopenia.
