Upregulation of FHL1, SPNS3, and MPZL2 predicts poor prognosis in pediatric acute myeloid leukemia patients with FLT3-ITD mutation.

ABSTRACT

Chromosomal translocations and gene mutations are characteristics of the genomic profile of acute myeloid leukemia (AML). We aim to identify a gene signature associated with poor prognosis in AML patients with FLT3-ITD compared to AML patients with NPM1/CEBPA mutations. RNA-sequencing (RNA-Seq) count data were downloaded from the UCSC Xena browser. Samples were grouped by their mutation status into high and low-risk groups. Differential gene expression (DGE), machine learning (ML) and survival analyses were performed. A total of 471 differentially expressed genes (DEGs) were identified, of which 16 DEGs were used as features for the prediction of mutation status. An accuracy of 92% was obtained from the ML model. FHL1, SPNS3, and MPZL2 were found to be associated with overall survival in FLT3-ITD samples. FLT3-ITD mutation confers an indicative gene expression profile different from NPM1/CEBPA mutation, and the expression of FHL1, SPSN3, and MPZL2 can serve as prognostic indicators of unfavorable disease.