Excessive Serine from the Bone Marrow Microenvironment Impairs Megakaryopoiesis and Thrombopoiesis in Multiple Myeloma

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 13

PMID 37055385

Authors

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

Soon will be listed here.

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.

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