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.

Keywords:

• Acute myeloid leukemia
• FLT3-ITD
• CEBPA
• NPM1
• prognostic indicators

Disclosure statement

Authors have no conflict of interest to declare.

Additional information

Funding

The work reported herein was made possible through funding by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the Mid-Career Scientist Programme from the South African National Treasury. The South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation of South Africa (Grant ID 64751) also supported this work; the Poliomyelitis Research Foundation; South African National Research Foundation.