Title:SFXN3 is Associated with Poor Clinical Outcomes and Sensitivity to the
Hypomethylating Therapy in Non-M3 Acute Myeloid Leukemia Patients
Volume: 23
Issue: 5
关键词:
急性髓系白血病（AML），SFXN3（铁屈蛋白3），DNA甲基化，表观遗传学，低甲基化治疗结果。
摘要:
Background: 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.
Objective: In this study, we hypothesized that SFXN3 indicates a poor prognosis and suggested tailored
treatment for AML patients.
Methods: 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.
Results: 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.
Conclusion: 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.
