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

Leuk Lymphoma. 2022 Aug;63(8):1897-1906. doi: 10.1080/10428194.2022.2045594. Epub 2022 Mar 6.

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; CEBPA; FLT3-ITD; NPM1; prognostic indicators.

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Child
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins / genetics
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / genetics
  • Muscle Proteins / genetics
  • Mutation
  • Nuclear Proteins* / genetics
  • Nucleophosmin
  • Prognosis
  • Up-Regulation
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Cell Adhesion Molecules
  • FHL1 protein, human
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • MPZL2 protein, human
  • Muscle Proteins
  • Nuclear Proteins
  • Nucleophosmin
  • SPNS3 protein, human