近日，美国希望之城贝克曼研究所教授Jianjun Chen等研究人员合作发现，m⁶A阅读器IGF2BP2调节谷氨酰胺代谢并且是急性骨髓性白血病的治疗靶标。该项研究成果于2022年10月27日在线发表在《癌细胞》杂志上。

Title: The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia

Author: Hengyou Weng, Feng Huang, Zhaojin Yu, Zhenhua Chen, Emily Prince, Yalin Kang, Keren Zhou, Wei Li, Jiacheng Hu, Chen Fu, Tursunjan Aziz, Hongzhi Li, Jingwen Li, Ying Yang, Li Han, Subo Zhang, Yuelong Ma, Mingli Sun, Huizhe Wu, Zheng Zhang, Mark Wunderlich, Sean Robinson, Daniel Braas, Johanna ten Hoeve, Bin Zhang, Guido Marcucci, James C. Mulloy, Keda Zhou, Hong-Fang Tao, Xiaolan Deng, David Horne, Minjie Wei, Huilin Huang, Jianjun Chen

Issue&Volume: 2022-10-27

Abstract: N6-Methyladenosine (m6A) modification and its modulators play critical roles and show promise as therapeutictargets in human cancers, including acute myeloid leukemia (AML). IGF2BP2 was recentlyreported as an m6A binding protein that enhances mRNA stability and translation. However, its functionin AML remains largely elusive. Here we report the oncogenic role and the therapeutictargeting of IGF2BP2 in AML. High expression of IGF2BP2 is observed in AML and associates with unfavorable prognosis. IGF2BP2 promotes AMLdevelopment and self-renewal of leukemia stem/initiation cells by regulating expressionof critical targets (e.g., MYC, GPT2, and SLC1A5) in the glutamine metabolism pathways in an m6A-dependent manner. Inhibiting IGF2BP2 with our recently identified small-moleculecompound (CWI1-2) shows promising anti-leukemia effects in vitro and in vivo. Collectively, our results reveal a role of IGF2BP2 and m6A modification in amino acid metabolism and highlight the potential of targeting IGF2BP2as a promising therapeutic strategy in AML.

DOI: 10.1016/j.ccell.2022.10.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00495-0