Li Jingyi, Kang Hui
Department of Hematology, Shanxi Maternal and Child Health Hospital, No. 13, Xinmin North Street, Taiyuan, 030000, China.
Clin Exp Med. 2025 Apr 29;25(1):129. doi: 10.1007/s10238-025-01669-0.
Methyltransferase 16 (METTL16) functions as an oncogene in various cancer, including leukemia. However, the role of METTL16 in acute myeloid leukemia (AML) is scarcely reported. The present study aimed to investigate the potential of METTL16 in AML.
RT-qPCR was used to METTL16 expression in AML patients and healthy control. m6A levels was determined using m6A assay. Methylated RNA immunoprecipitation (MeRIP) assay applied for determining m6A hypermethylation of T cell factor 1 (TCF-1) transcripts in AML cells. Chimeric antigen receptor (CAR)-T-cell functions were analyzed using flow cytometry.
METTL16 is upregulated in AML patients. High levels of METTL16 were associated with poor prognosis of AML patients. Functionally, METTL16 deficiency promoted the persistence and tumor-killing ability of CAR-T cells. Moreover, METTL16 deficiency promoted the differentiation of CAR-T cells into TCF-1 precursor exhausted T cells (T). METTL16 mediated the m6A modification of TCF-1 and inhibited its mRNA expression and stability. TCF-1 deficiency promoted the exhaustion and inhibited the self-renewal ability of T cells.
Collectively, METTL16 deficiency promoted the persistence of CAR-T cells and memory formation in AML. Therefore, targeting METTL16 may stimulate the anti-tumor immunity in AML.
甲基转移酶16（METTL16）在包括白血病在内的多种癌症中发挥癌基因作用。然而，METTL16在急性髓系白血病（AML）中的作用鲜有报道。本研究旨在探究METTL16在AML中的潜在作用。
采用RT-qPCR检测AML患者和健康对照中METTL16的表达。使用m6A检测法测定m6A水平。应用甲基化RNA免疫沉淀（MeRIP）试验测定AML细胞中T细胞因子1（TCF-1）转录本的m6A高甲基化。使用流式细胞术分析嵌合抗原受体（CAR）-T细胞功能。
METTL16在AML患者中上调。高水平的METTL16与AML患者的不良预后相关。在功能上，METTL16缺陷促进了CAR-T细胞的持久性和肿瘤杀伤能力。此外，METTL16缺陷促进了CAR-T细胞向TCF-1前体耗竭性T细胞（T）的分化。METTL16介导了TCF-1的m6A修饰并抑制其mRNA表达和稳定性。TCF-1缺陷促进了T细胞的耗竭并抑制其自我更新能力。
总体而言，METTL16缺陷促进了AML中CAR-T细胞的持久性和记忆形成。因此，靶向METTL16可能会刺激AML中的抗肿瘤免疫。
