Integrated Genomic and Transcriptomic Analysis of Thrombosis-Associated Pathways in Acute Myeloid Leukemia

Background Thromboembolic complications represent a significant clinical challenge in acute myeloid leukemia (AML), contributing to morbidity and complicating disease management. Although cancer-associated thrombosis (CAT) is well established,the molecular mechanisms linking thrombosis-associated pathways with AML biology has limited information and poorly understood. Aim : This study aimed to investigate the genomic and transcriptomic landscape of thrombosis-associated genes in AML and their potential biological interaction with leukemogenic pathways. Methods Genomic and clinical data from The Cancer Genomic Atlas (TCGA) AML cohort of 200 patients were analyzed using cBioPortal. A panel of 27 thrombosis-associated genes involved in coagulation, platelet activation, endothelial regulation, and fibrinolysis was identified and selected. Genomic alterations were assessed and mutation co-occurrence with AML driver genes was evaluated using OncoPrint. Protein–protein interaction (PPI) networks were constructed with STRING, and functional enrichment analysis was performed by Enrichr. Gene expression validation was conducted using GEPIA, integrating TCGA and GTEx datasets. Survival analysis was performed using Kaplan–Meier estimation and p-value< 0.05 was statistically significant. Results Thrombosis-associated genes demonstrated measurable genomic alterations, including mRNA expression changes and copy number variations majorly in genes F2,F3,F10,P2RY12,and SERPINE1. However, these genes showed limited statistically significant co-occurrence with canonical AML driver mutations with SERPINE1 and FLT3 (log2 odds ratio =0.918;p >0.05) and P2RY12 and RUNX1 (log2 odds ratio =0.272;p>0.001).The PPI network analysis revealed two distinct clusters corresponding to thrombosis-related and leukemogenic genes, with limited bridging interactions involving RUNX1,FLT3 and platelet-associated genes ITGA2B,ITGB3 and ITGA2B respectively. Functional enrichment analysis identified significant pathways related to complement and coagulation cascades, platelet activation, and fibrin clot formation. The gene expression analysis revealed low expression of classical coagulation factors (F2,F10) and moderate expression of platelet activation, endothelial interaction, and fibrinolysis-related genes. Survival analysis showed no significant association between thrombosis gene alterations and overall survival. Conclusion Thrombosis-associated genes in AML form a functionally coherent network that operates largely independently of canonical driver mutations but may contribute to a pro-thrombotic microenvironment initiation through platelet activation, endothelial signaling, and fibrinolysis regulation. These findings showed the importance of tumor–microenvironment interactions in AML-associated thrombosis and provide a basis for future studies exploring predictive biomarkers and therapeutic targets.