背景:DNA甲基化在急性髓细胞性白血病(AML)的发生和发展中起关键作用。线粒体丝氨酸转运蛋白,SFXN3对单碳代谢和DNA甲基化至关重要。然而,尚未报道SFXN3对AML发生和进展的影响.
目的:在本研究中,我们假设SFXN3提示预后不良,并建议针对AML患者进行量身定制的治疗.
方法:我们使用GEPIA和TCGA数据库数据来分析SFXN3的表达及其与AML患者生存的相关性。RT-qPCR用于检测我们登记的AML患者和志愿者中的SFXN3水平。此外,使用全基因组亚硫酸氢盐测序(WGBS)来检测个体中的基因组甲基化水平。
结果:通过TCGA和GEPIA数据库,我们发现SFXN3在AML患者中富集,预测更短的生存率。此外,我们证实SFXN3主要在AML患者中过度表达,尤其是非M3患者,并且发现非M3型AML患者的高SFXN3与不良结局和频繁的母细胞相关。有趣的是,接受低甲基化治疗的高SFXN3水平的非M3AML患者的CR比率较高.最后,我们发现SFXN3可以促进非M3型AML患者的转录起始位点(TSS)DNA甲基化.发现这些位点聚集在多个重要细胞功能中,并经常伴有DNMT3A和NPM1中的突变。
结论:结论:SXFN3在非M3AML患者的进展和超甲基化中起重要作用,并且可能是指示低甲基化疗法的高CR率的潜在生物标志物。
DNA hypermethylation plays a critical role in the occurrence and progression of acute myeloid leukemia (AML). The mitochondrial serine transporter, SFXN3, is vital for onecarbon metabolism and DNA methylation. However, the impact of SFXN3 on the occurrence and progression of AML has not been reported yet.
In this study, we hypothesized that SFXN3 indicates a poor prognosis and suggested tailored treatment for AML patients.
We used GEPIA and TCGA repository data to analyze the expression of SFXN3 and its correlation with survival in AML patients. RT-qPCR was used to detect the SFXN3 level in our enrolled AML patients and volunteers. Additionally, Whole Genome Bisulfite Sequencing (WGBS) was used to detect the genomic methylation level in individuals.
Through the TCGA and GEPIA databases, we found that SFXN3 was enriched in AML patients, predicting shorter survival. Furthermore, we confirmed that SFXN3 was primarily overexpressed in AML patients, especially non-M3 patients, and that high SFXN3 in non-M3 AML patients was found to be associated with poor outcomes and frequent blast cells. Interestingly, non-M3 AML patients with high SFXN3 levels who received hypomethylating therapy showed a higher CR ratio. Finally, we found that SFXN3 could promote DNA methylation at transcription start sites (TSS) in non-M3 AML patients. These sites were found to be clustered in multiple vital cell functions and frequently accompanied by mutations in DNMT3A and NPM1.
In conclusion, SXFN3 plays an important role in the progression and hypermethylation in non-M3 AML patients and could be a potential biomarker for indicating a high CR rate for hypomethylating therapy.