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Excessive serine from the bone marrow microenvironment impairs megakaryopoiesis and thrombopoiesis in Multiple Myeloma

Author

Listed:
  • Chunmei Kuang

    (Central South University
    Central South University)

  • Meijuan Xia

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Gang An

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • CuiCui Liu

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Cong Hu

    (Central South University
    Central South University)

  • Jingyu Zhang

    (Central South University
    Central South University)

  • Zhenhao Liu

    (Central South University
    Central South University)

  • Bin Meng

    (Central South University
    Central South University)

  • Pei Su

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jiliang Xia

    (Central South University
    Central South University)

  • Jiaojiao Guo

    (Central South University
    Central South University)

  • Yinghong Zhu

    (Central South University
    Central South University)

  • Xing Liu

    (Central South University
    Central South University)

  • Xuan Wu

    (Central South University
    Central South University)

  • Yi Shen

    (Central South University)

  • Xiangling Feng

    (Central South University)

  • Yanjuan He

    (Central South University)

  • Jian Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lugui Qiu

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jiaxi Zhou

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Wen Zhou

    (Central South University
    Central South University)

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.

Suggested Citation

  • 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 Fen, 2023. "Excessive serine from the bone marrow microenvironment impairs megakaryopoiesis and thrombopoiesis in Multiple Myeloma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37699-z
    DOI: 10.1038/s41467-023-37699-z
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    as
    1. Jiliang Xia & Jingyu Zhang & Xuan Wu & Wanqing Du & Yinghong Zhu & Xing Liu & Zhenhao Liu & Bin Meng & Jiaojiao Guo & Qin Yang & Yihui Wang & Qinglin Wang & Xiangling Feng & Guoxiang Xie & Yi Shen & Y, 2022. "Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
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