急性髓细胞性白血病(AML)是一种起源于骨髓造血干细胞的恶性疾病。最近的研究表明,某些基因突变通过影响肿瘤细胞的代谢机制,促进肿瘤细胞的存活并影响患者的预后。RAS基因突变在AML中普遍存在,RAS信号通路与许多代谢通路密切相关。然而,不同RAS基因突变对AML细胞代谢的影响尚不清楚.
■本研究的主要目的是探讨RAS基因突变对肿瘤细胞代谢途径的影响。
■在这项研究中,我们首先使用携带突变基因的逆转录病毒制备具有RAS基因突变的Ba/F3细胞系,然后比较RAS基因突变前后Ba/F3细胞的全转录组数据,发现NRASQ61K和KRASG12V突变后差异表达基因。
■我们在NRASQ61K和KRASG12V突变后发现了总共1899个差异表达基因。1089个基因参与代谢过程,其中167个基因富集在代谢相关途径中。在代谢相关途径中,差异基因与脂质代谢途径相关。此外,通过比较群体,我们发现DGKzeta和PLA2G4A基因在甘油磷脂代谢途径中的表达显著上调。
■总而言之,本研究发现,Ba/F3细胞中RAS基因突变与甘油磷脂代谢途径密切相关,这可能有助于新的精准治疗策略以及新的AML治疗药物的开发和应用。
UNASSIGNED: 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. RAS gene mutations are prevalent in AML, and the RAS signaling pathway is closely related to many metabolic pathways. However, the effects of different RAS gene mutations on AML cell metabolism are unclear.
UNASSIGNED: The main purpose of this study was to explore the effect of RAS gene mutation on the metabolic pathway of tumor cells.
UNASSIGNED: In this study, we first used a retrovirus carrying a mutant gene to prepare Ba/F3 cell lines with RAS gene mutations, and then compared full-transcriptome data of Ba/F3 cells before and after RAS gene mutation and found that differentially expressed genes after NRASQ61K and KRASG12V mutation.
UNASSIGNED: We found a total of 1899 differentially expressed genes after NRASQ61K and KRASG12V 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 DGKzeta and PLA2G4A genes in the glycerophospholipid metabolism pathway was significantly upregulated.
UNASSIGNED: In conclusion, our study revealed that RAS 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.