Runt-related transcription factor 1 gene (RUNX1), also known as acute myeloid leukemia 1 protein (AML1), plays a critical role in the pathogenesis of AML. One of leukemia's most frequently mutated genes is RUNX1/AML1, which is related to a poor prognosis in AML. Researchers and clinicians can design personalized medicines and enhance diagnosis by identifying biomarkers linked to genetic mutations. In the current study, we used TCGA-Acute Myeloid Leukemia (AML) cohort's genomic and transcriptome data. We analyzed RUNX1 mutated AML patients to non-mutated patients using an integrated, multi-omics, multi-database analysis of exome and transcriptomics data. The mutation landscape of several genes, including RUNX1 mutations, was revealed by TCGA-AML data from multi-center high-throughput exome sequencing. Finally, we identified the gene signature associated with RUNX1 mutations, including prognostic genes that significantly impacted the overexpression of the RUNX1 pathway in RUNX1 mutated AML patients. Our findings may help diagnose AML patients with RUNX1 mutations early.