IMPDH2是GTP从头合成途径的限速酶，在肿瘤中具有关键作用；然而，IMPDH2 活性在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中的具体机制仍不清楚。本研究旨在探讨IMPDH2在DLBCL中的潜在机制，以及其可能参与双重打击淋巴瘤（DHL），即涉及MYC和BCL2和/或BCL6易位的病例。利用单细胞测序和生物信息学分析来筛选对于IMPDH2。通过多重免疫荧光分析探讨IMPDH2的差异表达及其与预后的相关性。利用CCK8、EdU、克隆形成实验和动物模型分析抑制IMPDH2后生物学行为的变化。通过Western blot和多重免疫荧光解释IMPDH2在DLBCL中的潜在机制。通过单细胞测序构建预后风险模型，将IMPDH2鉴定为DHL相关基因。 IMPDH2 在细胞系和组织中高表达，与患者预后不良相关，是一个独立的预后因素。体外和体内实验表明，抑制IMPDH2可显着抑制DHL细胞增殖。流式细胞术显示细胞凋亡和周期停滞。 Western blot结果提示c-Myc通过IMPDH2调节PI3K/AKT/mTOR信号通路的激活促进DHL肿瘤的发生。此外，多重免疫荧光显示肿瘤微环境中 T 细胞浸润减少，同时表现出 IMPDH2 和 PD-L1 的高表达。我们的结果表明，IMPDH2 在 DHL 中充当肿瘤促进因子。这一发现有望对这些患者的发病机制产生新的见解，从而确定潜在的治疗靶点。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

IMPDH2 is the rate-limiting enzyme of the de novo GTP synthesis pathway and has a key role in tumors; however, the specific mechanism underlying IMPDH2 activity in diffuse large B cell lymphoma (DLBCL) is still undetermined. This study aims to explore the potential mechanism of IMPDH2 in DLBCL, and its possible involvement in double-hit lymphoma (DHL), i.e., cases with translocations involving MYC and BCL2 and/or BCL6.Using single-cell sequencing and bioinformatics analysis to screen for IMPDH2. Exploring the differential expression of IMPDH2 and its correlation with prognosis through multiplexed immunofluorescence analysis. Using CCK8, EdU, clone formation assay, and animal model to analyze biological behavior changes after inhibiting IMPDH2. Explaining the potential mechanism of IMPDH2 in DLBCL by Western blot and multiplexed immunofluorescence.Prognostic risk model was constructed by single-cell sequencing, which identified IMPDH2 as a DHL-related gene. IMPDH2 was highly expressed in cell lines and tissues, associated with poor patient prognosis and an independent prognostic factor. In vitro and in vivo experiments showed that IMPDH2 inhibition significantly inhibited DHL cell proliferation. Flow cytometry showed apoptosis and cycle arrest. Western blot results suggested that c-Myc regulated the activation of PI3K/AKT/mTOR signaling pathway by IMPDH2 to promote tumor development in DHL. Moreover, multiplex immunofluorescence revealed decreased T-cell infiltration within the tumor microenvironment exhibiting concurrent high expression of IMPDH2 and PD-L1.Our results suggest that IMPDH2 functions as a tumor-promoting factor in DHL. This finding is expected to generate novel insights into the pathogenesis of these patients, thereby identifying potential therapeutic targets.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.