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在急性髓系白血病中鉴定出的RAS基因突变影响甘油磷脂代谢途径。

Mutations of RAS genes identified in acute myeloid leukemia affect glycerophospholipid metabolism pathway.

作者信息

Liang Tianqi, Kong Yanxiang, Xue Hongman, Wang Wenqing, Li Chunmou, Chen Chun

机构信息

Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.

Department of Reproductive Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.

出版信息

Front Oncol. 2023 Nov 14;13:1280192. doi: 10.3389/fonc.2023.1280192. eCollection 2023.

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is a malignant disease originating from myeloid hematopoietic stem cells. Recent studies have shown that certain gene mutations promote tumor cell survival and affect the prognosis of patients by affecting metabolic mechanisms in tumor cells. gene mutations are prevalent in AML, and the signaling pathway is closely related to many metabolic pathways. However, the effects of different gene mutations on AML cell metabolism are unclear.

OBJECTIVES

The main purpose of this study was to explore the effect of gene mutation on the metabolic pathway of tumor cells.

METHODS

In this study, we first used a retrovirus carrying a mutant gene to prepare Ba/F3 cell lines with gene mutations, and then compared full-transcriptome data of Ba/F3 cells before and after gene mutation and found that differentially expressed genes after NRAS and KRAS mutation.

RESULTS

We found a total of 1899 differentially expressed genes after NRAS and KRAS mutation. 1089 of these genes were involved in metabolic processes, of which 167 genes were enriched in metabolism-related pathways. In metabolism-related pathways, differential genes were associated with the lipid metabolism pathway. Moreover, by comparing groups, we found that the expression of the and genes in the glycerophospholipid metabolism pathway was significantly upregulated.

CONCLUSION

In conclusion, our study revealed that gene mutation is closely related to the glycerophospholipid metabolism pathway in Ba/F3 cells, which may contribute to new precision therapy strategies and the development and application of new therapeutic drugs for AML.

摘要

背景

急性髓系白血病(AML)是一种起源于髓系造血干细胞的恶性疾病。最近的研究表明,某些基因突变可促进肿瘤细胞存活,并通过影响肿瘤细胞的代谢机制来影响患者的预后。基因突变在AML中很普遍,且 信号通路与许多代谢途径密切相关。然而,不同的 基因突变对AML细胞代谢的影响尚不清楚。

目的

本研究的主要目的是探讨 基因突变对肿瘤细胞代谢途径的影响。

方法

在本研究中,我们首先使用携带突变基因的逆转录病毒制备具有 基因突变的Ba/F3细胞系,然后比较Ba/F3细胞在 基因突变前后的全转录组数据,发现NRAS和KRAS突变后有差异表达基因。

结果

我们发现NRAS和KRAS突变后共有1899个差异表达基因。其中1089个基因参与代谢过程,其中167个基因富集于代谢相关途径。在代谢相关途径中,差异基因与脂质代谢途径相关。此外,通过比较各组,我们发现甘油磷脂代谢途径中的 和 基因表达显著上调。

结论

总之,我们的研究表明 基因突变与Ba/F3细胞中的甘油磷脂代谢途径密切相关,这可能有助于为AML制定新的精准治疗策略以及开发和应用新的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb48/10682766/a482fd0d6653/fonc-13-1280192-g001.jpg

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