Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients.
Peggy KanellouIlias Georgakopoulos-SoaresApostolos ZaravinosPublished in: Cancers (2023)
Acute myeloid leukemia (AML) is a heterogeneous and complex disease concerning molecular aberrations and prognosis. RUNX1/RUNX1T1 is a fusion oncogene that results from the chromosomal translocation t(8;21) and plays a crucial role in AML. However, its impact on the transcriptomic profile of different age groups of AML patients is not completely understood. Here, we investigated the deregulated gene expression (DEG) profiles in adult and pediatric RUNX1/RUNX1T1-positive AML patients, and compared their functions and regulatory networks. We retrospectively analyzed gene expression data from two independent Gene Expression Omnibus (GEO) datasets (GSE37642 and GSE75461) and computed their differentially expressed genes and upstream regulators, using limma , GEO2Enrichr , and X2K . For validation purposes, we used the TCGA-LAML (adult) and TARGET-AML (pediatric) patient cohorts. We also analyzed the protein-protein interaction (PPI) networks, as well as those composed of transcription factors (TF), intermediate proteins, and kinases foreseen to regulate the top deregulated genes in each group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were further performed for the DEGs in each dataset. We found that the top upregulated genes in (both adult and pediatric) RUNX1/RUNX1T1-positive AML patients are enriched in extracellular matrix organization, the cell projection membrane, filopodium membrane, and supramolecular fiber. Our data corroborate that RUNX1/RUNX1T1 reprograms a large transcriptional network to establish and maintain leukemia via intricate PPI interactions and kinase-driven phosphorylation events.
Keyphrases
- transcription factor
- acute myeloid leukemia
- gene expression
- end stage renal disease
- genome wide identification
- newly diagnosed
- genome wide
- chronic kidney disease
- ejection fraction
- protein protein
- extracellular matrix
- peritoneal dialysis
- prognostic factors
- small molecule
- cell therapy
- acute lymphoblastic leukemia
- computed tomography
- patient reported outcomes
- deep learning
- single molecule
- quantum dots
- bone marrow
- dna binding
- machine learning
- young adults
- magnetic resonance
- electronic health record
- rna seq
- heat shock protein
- childhood cancer