In April 2023, a study led by Professors Zhou Wen from Central South University was published in the top international academic journal Nature Communications (IF=16.6), titled "Excessive serine from the bone marrow microenvironment impairs megakaryopiaisis and thrombosis in Multiple Myeloma". This study provides valuable insights into new treatment methods for improving thrombocytopenia in patients with multiple myeloma and ultimately improving patient prognosis. It was recently selected as one of the "Top 10 Research Advances in Hematology in China in 2023".
Thrombocytopenia, a major complication in multiple myeloma (MM) patients, is associated with poor prognosis. However, the factors contributing to thrombocytopenia in MM and their significance are not well understood. Recent research has identified excessive serine released from MM cells into the bone marrow microenvironment as a metabolic factor that suppresses megakaryopoiesis and thrombopoiesis, leading to thrombocytopenia. Understanding the role of serine in MM-associated thrombocytopenia could provide insights into potential therapeutic strategies.
The study investigated the impact of excessive serine on thrombocytopenia in MM patients. Research found that serine, transported into MKs through SLC38A1, downregulates Supervillin (SVIL) via SAM-mediated tri-methylation of H3K9, resulting in impaired megakaryopoiesis. Inhibition of serine utilization or treatment with thrombopoietin (TPO) enhanced megakaryopoiesis and thrombopoiesis, suppressing MM progression. The study also demonstrated that serine supplementation in the bone marrow microenvironment inhibited megakaryopoiesis and thrombopoiesis in vitro and led to sustained higher platelet counts in mice.
Thrombocytopenia in MM patients was found to be associated with poor overall survival and progression-free survival, particularly in patients with advanced stages of the disease. The number of megakaryocytes was significantly decreased in MM patients with low platelet counts, suggesting impaired megakaryopoiesis. Moreover, the study showed an increased apoptotic rate of platelets in MM patients, which could contribute to thrombocytopenia.
Excessive serine in the bone marrow microenvironment acts as a key metabolic regulator of thrombocytopenia in MM. The study identified serine as a potential therapeutic target, and restricting serine uptake through the inhibition of SLC38A1 was shown to prevent thrombocytopenia in a mouse model of MM. These findings offer the possibility of targeted interventions to improve thrombocytopenia in MM patients and potentially impact disease progression.
Excessive serine released from MM cells impairs megakaryopoiesis and thrombopoiesis, leading to thrombocytopenia in MM patients. Targeting serine metabolism or uptake, particularly through inhibition of SLC38A1, could serve as a potential therapeutic strategy. Further research in this area may provide valuable insights for the development of novel treatments aimed at improving thrombocytopenia in MM patients and ultimately enhancing patient outcomes.
