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胰岛素样生长因子 1 受体通过 NK 细胞激活抑制急性髓系白血病细胞的增殖。

Insulin-like growth factor 1 receptor inhibits the proliferation of acute myeloid leukaemia cells via NK cell activation.

机构信息

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

出版信息

Ann Hematol. 2023 Sep;102(9):2353-2364. doi: 10.1007/s00277-023-05378-0. Epub 2023 Jul 31.

DOI:10.1007/s00277-023-05378-0
PMID:37522970
Abstract

Acute myeloid leukaemia (AML) denotes a heterogeneous category of cancers occurring within the bone marrow that are initiated by the unrestricted proliferation of haematopoietic stem cells. Various factors effectuate the dysregulation of AML cell proliferation; for instance, the upregulation of insulin-like growth factor 1 receptor (IGF1R) within AML cells influences their proliferation. However, there is a current dearth of research assessing the association between IGF1R and prognostic risk as well as its potential as an AML immunotherapeutic. This study aims to elucidate the role of IGF1R in AML progression and evaluate its prognostic value. To this end, RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database was analysed to compare IGF1R expression between AML and normal tissues. Moreover, a Kaplan-Meier survival analysis was performed to determine whether IGF1R expression correlates with patient overall survival (OS). TCGA data revealed upregulated IGF1R expression in the peripheral blood of AML patients compared to that in healthy individuals. Meanwhile, IGF1R expression positively correlates with patient OS. Additionally, elevated IGF1R expression promotes NK cell expansion and enhances its functional activation, thereby inhibiting AML cell proliferation. Collectively, these findings highlight the clinical potential of IGF1R in the effective treatment of AML through the activation of NK cell proliferation and function and suggest that it may represent a potential predictive marker of AML prognosis.

摘要

急性髓系白血病(AML)是一种发生在骨髓中的异质性癌症类别,由造血干细胞的不受限制增殖引发。多种因素导致 AML 细胞增殖失调;例如,AML 细胞中胰岛素样生长因子 1 受体(IGF1R)的上调会影响其增殖。然而,目前缺乏评估 IGF1R 与预后风险之间的关联及其作为 AML 免疫治疗的潜力的研究。本研究旨在阐明 IGF1R 在 AML 进展中的作用,并评估其预后价值。为此,分析了来自癌症基因组图谱(TCGA)数据库的 RNA 测序(RNA-seq)数据,以比较 AML 和正常组织中的 IGF1R 表达。此外,还进行了 Kaplan-Meier 生存分析,以确定 IGF1R 表达是否与患者总生存期(OS)相关。TCGA 数据显示,AML 患者外周血中的 IGF1R 表达高于健康个体。同时,IGF1R 表达与患者 OS 呈正相关。此外,升高的 IGF1R 表达促进 NK 细胞扩增并增强其功能激活,从而抑制 AML 细胞增殖。总之,这些发现突出了 IGF1R 通过激活 NK 细胞增殖和功能在 AML 有效治疗中的临床潜力,并表明它可能代表 AML 预后的潜在预测标志物。

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