小柯机器人

蛋白质精氨酸甲基转移酶(PRMT)7缺失诱导的甘氨酸代谢重编程，可选择性根除慢性髓性白血病(CML)患者的白血病干细胞(LSC)，这一成果由中山大学Jingxuan Pan和暨南大学Yanli Jin小组合作经过不懈努力而取得。这一研究成果发表在2022年5月3日出版的国际学术期刊《细胞-代谢》上。

研究人员探究了PRMT7在维持CML患者LSC中的作用，因为它在PRMT家族中具有独特的功能。Prmt7缺失以及PRMT7小分子特异性抑制剂的开发和测试表明，在CML小鼠模型和人类原代CML CD34^₊细胞中，靶向PRMT7可延缓白血病发展并损害LSC的自我更新，而不影响正常造血。

从机制上讲，PRMT7缺失导致甘氨酸脱羧酶表达减少，导致甘氨酸代谢重新编程以产生甲基乙二醛，这对LSC是有害的。这些发现将组蛋白精氨酸甲基化与甘氨酸代谢联系起来，同时表明PRMT7可作为根除CML中LSCs的潜在治疗靶点。

据了解，之前的研究报道了蛋白质精氨酸甲基转移酶(PRMT)家族中各种成员在白血病进展中的作用，这些成员参与表观遗传调控。

附：英文原文

Title: Loss of PRMT7 reprograms glycine metabolism to selectively eradicate leukemia stem cells in CML

Author: Chang Liu, Waiyi Zou, Danian Nie, Shuyi Li, Chen Duan, Min Zhou, Peilong Lai, Shengyong Yang, Sen Ji, Yangqiu Li, Mei Mei, Shilai Bao, Yanli Jin, Jingxuan Pan

Issue&Volume: 2022-05-03

Abstract: Our group has reported previously on the role of various members of the protein argininemethyltransferase (PRMT) family, which are involved in epigenetic regulation, in theprogression of leukemia. Here, we explored the role of PRMT7, given its unique functionwithin the PRMT family, in the maintenance of leukemia stem cells (LSCs) in chronicmyeloid leukemia (CML). Genetic loss of Prmt7, and the development and testing of a small-molecule specific inhibitor of PRMT7,showed that targeting PRMT7 delayed leukemia development and impaired self-renewalof LSCs in a CML mouse model and in primary CML CD34+ cells from humans without affecting normal hematopoiesis. Mechanistically, loss ofPRMT7 resulted in reduced expressions of glycine decarboxylase, leading to the reprogramingof glycine metabolism to generate methylglyoxal, which is detrimental to LSCs. Thesefindings link histone arginine methylation with glycine metabolism, while suggestingPRMT7 as a potential therapeutic target for the eradication of LSCs in CML.

DOI: 10.1016/j.cmet.2022.04.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00131-0

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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