Effect Of SFXN3 On Genomic DNA Methylation And The Prognosis In Non-M3 Acute Myeloid Leukemia Patients

Objective: To observe the expression level of SFXN3 in AML patients and the effect of SFXN3 on the prognosis and genomic DNA methylation,explore whether SFXN3 can be a potential biomarker for predicting the prognosis of AML patients and the sensitivity to hypomethylating therapy.Methods: GEPIA and TCGA repository data were used to preliminary analyze the expression and survival of SFXN3 in AML patients.Then,the bone marrow samples from 33 newly diagnosed AML patients and 23 normal people were collected,RT-q PCR was used to detect the SFXN3 level in our enrolled AML patients and volunteers,observed the relationship between SFXN3 and the risk of disease,the proportion of blast cells,the results of second-generation sequencing,the chromosome karyotype,and the sensitivity to hypomethylating therapy.Whole Genome Bisulfite Sequencing(WGBS)was used to detect the genomic methylation level of individuals.Differentially methylated genes were identified by the threshold of a p-value ≤ 0.05 as well as the absolute delta cutoff between the two groups ≥ 10%,GO and KEGG pathway enrichment analyses of differentially methylated genes were performed.Results: Through the TCGA and GEPIA databases,we found that SFXN3 was enriched in AML patients(P<0.05)and high SFXN3 predicted shorter survival(P<0.05).Further,we confirmed in our enrolled individuals that SFXN3 was primarily overexpressed in AML patients(P<0.01),especially non-M3 patients(P<0.05),and high SFXN3 Non-M3 patients always suffered a poor outcome risk(P<0.05),frequent blast cells(P<0.05)and often accompanied by mutations in DNMT3 A and NPM1(P<0.05);however,the expression of SFXN3 in M3 patients was not significantly different from that in volunteers(P>0.05)and was lower than that in non-M3 patients(P<0.05).Interestingly,a higher CR ratio was observed in high SFXN3 Non-M3 patients who received hypomethylating therapy,while patients with low SFXN3 could not benefit from hypomethylating therapy.Finally,we found SFXN3 could promote the DNA methylation in Non-M3 AML patients at transcription start sites(TSS)(P<0.05)which clustered in multiple vital cell functions.Conclusion: In conclusion,we thought SXFN3 could promote the CPG methylation at TSS,plays an important role affecting the occurrence and progression of AML,which is associated with a poor clinical outcome and sensitivity to the hypomethylating therapy in Non-M3 AML patients,indicated that SFXN3 is a potential biomarker of evaluating tumor methylation enrichment and predicting the prognosis of the disease and provided a new direction for the pathogenesis of AML and the guidance of hypomethylating therapy.