蛋白精氨酸甲基转移酶5表达与非M3型急性髓系白血病疗效关系的临床观察

Clinical observation of the relationship between ARMT5 expression and therapeutic efficacy in non M3 AML patients

目的讨论蛋白精氨酸甲基转移酶5(PRMT5)与急性髓系白血病(AML)患者低甲基化药物(HMA)治疗敏感性的关系。方法通过GEPIA和TCGA数据库分析AML患者PRMT5表达及其与AML患者生存的关系。收集2020年1月至2023年10月收治的81例AML患者,包括50例非M3型患者和31例M3型患者。采用实时荧光定量PCR(qPCR)检测骨髓样本中PRMT5表达。采用全基因组重亚硫酸盐测序(WGBS)检测基因组甲基化水平。结果TCGA数据库中AML患者PRMT5表达显著高于健康对照人群(P<0.01);PRMT5高表达组患者总生存期更短(P=0.036)。进一步分析TCGA数据库,巩固期给予HMA后,PRMT5表达对无事件生存率(EFS)和OS的有明显影响(P<0.010)。81例新诊断AML患者PRMT5表达显著高于23例健康志愿者[3.25(1.69,5.16)vs.1.00(0.72,1.35),P<0.001]。非M3型AML患者PRMT5表达高于M3型患者[4.51(2.05,7.25)vs.2.01(1.53,3.35),(P<0.001)]。在非M3型AML患者中,PRMT5高表达与BM原始细胞百分率以及不良基因突变和高危患者比例更高有关(P<0.05)。与未接受HMA治疗患者比较,接受HMA治疗的PRMT5高表达非M3型AML患者CR率显著增加(P=0.003)。通过WGBS测序,PRMT5高表达组CpG岛甲基化比率以及转录起始位点、转录终止位点CpG岛甲基化比率高于PRMT5低表达组(P<0.001)。结论在非M3型AML患者中PRMT5高表达,PRMT5高表达预示着更多非M3型AML患者从HMA治疗中获益。PRMT5可能是评估肿瘤甲基化富集和预测疾病预后的潜在生物标志物。

Objective To discuss the relationship between protein arginine methyltransferase 5(PRMT5)and hypomethylating agents(HMA)treatment sensitivity in patients with acute myeloid leukemia(AML).Methods The expression of PRMT5 in AML patients and its relationship with survival were analyzed using GEPIA and TCGA databases.A total of 81 patients with AML admitted between January 2020 and October 2023 were collected,including 50 non-M3 patients and 31 M3 patients.Real time fluorescence quantitative PCR(qPCR)was used to detect PRMT5 expression in bone marrow samples.Genome-wide bisulfite sequencing(WGBS)was used to detect genomic methylation levels.Results The expression of PRMT5 in AML patients in the TCGA database was significantly higher than that in healthy controls(P<0.01).Patients with high expression of PRMT5 had shorter overall survival(P=0.036).Further analysis of TCGA database showed that PRMT5 expression significantly affected event-free survival(EFS)and OS after HMA was given in the consolidation period(P<0.01).The expression of PRMT5 in 81 newly diagnosed AML patients was significantly higher than that in 23 healthy volunteers[3.25(1.69,5.16)vs.1.00(0.72,1.35),P<0.001].The expression of PRMT5 in non-M3 AML patients was higher than that in M3 patients[4.51(2.05,7.25)vs.2.01(1.53,3.35),P<0.001].In non-M3 AML patients,high PRMT5 expression was associated with a higher percentage of BM original cells and a higher proportion of adverse gene mutations and high-risk patients(P<0.05).Non-m3 AML patients with high PRMT5 expression who received HMA had a significantly higher CR rate than patients who did not receive HMA(P=0.003).By WGBS sequencing,the CpG island methylation ratio and the CpG island methylation ratio at the transcription start and end sites in the PRMT5 high expression group were higher than those in the PRMT5 low expression group(P<0.001).Conclusion PRMT5 is significantly overexpressed in non-M3 AML patients,indicating that more non-M3 AML patients will benefit from HMA treatment.PRMT5 may be a potential biomarker for evaluating tumor methylation enrichment and predicting disease prognosis.