Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Geriatric Disorders, Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.
Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Br J Haematol. 2023 May;201(4):704-717. doi: 10.1111/bjh.18684. Epub 2023 Feb 8.
Amino acids in the bone marrow microenvironment (BMME) are a critical factor for multiple myeloma (MM) progression. Here, we have determined that proline is elevated in BMME of MM patients and links to poor prognosis in MM. Moreover, exogenous proline regulates MM cell proliferation and drug resistance. Elevated proline in BMME is due to bone collagen degradation and abnormal expression of the key enzyme of proline catabolism, proline dehydrogenase (PRODH). PRODH is downregulated in MM patients, mainly as a result of promoter hypermethylation with high expression of DNMT3b. Thus, overexpression of PRODH suppresses cell proliferation and drug resistance of MM and exhibits therapeutic potential for treatment of MM. Altogether, we identify proline as a key metabolic regulator of MM, unveil PRODH governing MM progression and provide a promising therapeutic strategy for MM treatment.
骨髓微环境（BMME）中的氨基酸是多发性骨髓瘤（MM）进展的关键因素。在这里，我们已经确定，脯氨酸在 MM 患者的 BMME 中升高，并与 MM 的不良预后相关。此外，外源性脯氨酸调节 MM 细胞增殖和耐药性。BMME 中脯氨酸的升高是由于骨胶原降解和脯氨酸分解代谢的关键酶脯氨酸脱氢酶（PRODH）的异常表达。PRODH 在 MM 患者中下调，主要是由于启动子超甲基化导致高表达 DNMT3b。因此，PRODH 的过表达抑制 MM 细胞的增殖和耐药性，具有治疗 MM 的潜在疗效。总之，我们确定脯氨酸是 MM 的关键代谢调节剂，揭示了 PRODH 调控 MM 进展，并为 MM 的治疗提供了一种有前途的治疗策略。
