In this study, we aimed at exploring and validating the prognostic value of PLA2G4A expression in patients with non-M3/nucleophosmin (NPM1) wildtype (WT) acute myeloid leukemia (AML) by using two independent datasets. Data from the Cancer Genome Atlas-acute myeloid leukemia (TCGA-LAML) and the therapeutically applicable research to generate effective treatments (TARGET)-AML were used to assess the prognostic value of PLA2G4A in NPM1-WT AML cases. Results showed that non-M3 AML cases had significantly increased PLA2G4A expression compared with normal peripheral blood samples. Patients with high PLA2G4A expression (separated by median gene expression) had a significantly shorter overall survival (OS) compared with the group with low PLA2G4A expression, in both TCGA-LAML and TARGET-AML. Multivariate analysis showed that high PLA2G4A expression was independently associated with shorter OS in 97 non-M3/NPM1-WT AML cases in TCGA-LAML (hazard ratio [HR]: 1.946, 95% confidence interval [CI]: 1.094-3.462, q = 0.036). The prognostic value was validated based on 120 primary non-M3/NPM1-WT AML cases in TARGET-AML (HR: 1.518, 95% CI: 1.037-2.223, q = 0.048). Therefore, PLA2G4A expression might serve as an independent prognostic marker in OS in patients with non-M3/NPM1 WT AML. Bioinformatic analysis identified that several proteins physically interacted with PLA2G4A, some of which have well-characterized oncogenic properties in AML, such as RUVBL2, cytoskeleton regulatory protein 1 (CAP1), signal transducer and activator of transcription 3 (STAT3), and MYCBP. Therefore, we hypothesized that PLA2G4A upregulation has multiple effects on the malignant phenotype of AML cells together with its partners. Future molecular studies are required to explore the detailed regulatory network involved.

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