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