Abstract

Abstract In this study, we aimed to explore and validate the prognostic value of PLA2G4A expression in patients with non-M3/NPM1 wildtype (WT) acute myeloid leukemia (AML) 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 PLA2G4A in NPM1-WT AML cases. A single-cell RNA-seq dataset that included 96 AML cells from a recurrent AML case was used to check the correlation between PLA2G4A expression and the functional state of AML cells. Results showed that non-M3 AML cases had significantly increased PLA2G4A expression compared to normal peripheral blood samples. Multivariate analysis showed that high PLA2G4A expression was independently associated with shorter OS in 97 non-M3/NPM1-WT AML cases in TCGA-LAML (HR: 1.932, 95%CI: 1.092-3.419, p=0.024). The prognostic value was validated based on 128 non-M3/NPM1-WT AML cases in TARGET-AML (HR: 1.894, 95%CI: 1.065-3.369, p=0.030). Single-cell RNA-seq data suggested that PLA2G4A expression was positively correlated with cell cycle progression of AML cells. Therefore, PLA2G4A expression might serve as an independent prognostic marker in OS in patients with non-M3/NPM1 WT AML. Its upregulation might confer malignant phenotype of AML cells at least partly by promoting cell cycle progression. Future molecular studies are required to explore other molecular pathways involved. Citation Format: Hansong Bai, Zeng Ming. Pla2g4a: A new cell cycle related gene in patients with non-M3/NPM1 wildtype acute myeloid leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 94.

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