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pmid:36980682
Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients.
Peggy Kanellou · Ilias Georgakopoulos-Soares · Apostolos Zaravinos
Cancers · 2023 doi:10.3390/cancers15061795
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "We assessed statistical differences in gene expression between RUNX1/RUNX1T1-positive and RUNX1/RUNX1T1-negative AML samples through the Mann–Whitney U test, with an adj. p < 0.05 as a threshold for statistical significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36980682", "locator": "sections[5] \"2.3. Statistical Analysis\" paragraph 2", "quote": "We assessed statistical differences in gene expression between RUNX1/RUNX1T1-positive and RUNX1/RUNX1T1-negative AML samples through the Mann–Whitney U test, with an adj. p < 0.05 as a threshold for statistical significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article [and its Supplementary Information Files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36980682", "locator": "sections[15] \"Data Availability Statement\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article [and its Supplementary Information Files]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36980682"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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