MPN-304: Identification of the Key Genes and Molecular Pathways in Essential Thrombocythemia Associated with JAK2V617F Mutation Using Bioinformatics Approach

Abstract

Introduction: JAK2V617F mutation is one of the most common driver mutations for essential thrombocythemia (ET), found in approximately 55% of patients. Thrombotic events were reported more often in JAK2V617F-positive patients than in JAK2V617F-negative patients. This study focused on identifying the differentially expressed genes (DEGs) in JAK2V617F ET. Method: The gene expression profiles of 6 ET patients (3 JAK2V617F-positive, 3 JAK2V617F-negative) and 5 healthy individuals (GSE55976) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs were identified using GEO2R. An adjusted p-value 1 were defined as the criteria for DEG. Gene ontology functional and pathway enrichment analyses of DEGs were performed using DAVID, and the protein–protein interaction network was constructed. Results: A total of 58 DEGs were identified in JAK2V617F ET compared to healthy controls. Of the 58 DEGs, 12 genes were commonly overexpressed in both JAK2V617F-positive and JAK1V617F-negative ET; 32 genes were overexpressed in JAK2V617F-positive, with no differences were found between JAK2V617F-negative ET and controls; and the remaining 14 genes were overexpressed only in JAK2V617F-positive ET (ANKRD13A, ATP6V0E1, HERPUD1, HLA-DRB3, IGK, KIAA0930, LTB, PILRA, PYCARD, RAB8B, SNAP23, SON, VCAN, YWHAB). GO analysis revealed that the 14 genes associated with JAK2V617F were significantly enriched in the components of biological processes (BP), including cell communication, leukocyte activation, and immune response. The cellular components (CC) category indicated an enrichment of genes associated with the membrane and cytoplasmic vesicle. The most significant GO terms describing molecular functions (MF) for the enriched genes were protein domain-specific binding and receptor binding. Pathway analysis revealed that most of the genes in this dataset were involved in immune system pathways, membrane trafficking pathways, and cell adhesion molecules (CAMs). Conclusion: This data manifested that the majority of the overexpressed genes in JAK2V617F ET were localized on the cell membrane and involved in cell communication and immune response. The cross-talk between inflammation and thrombosis was previously described. A more interesting finding in this dataset is that SNAP23 was identified as one of the highly connected genes. SNAP23 is known to regulate platelet granule secretion. This gives insight into SNAP23 as a potential therapeutic target in JAK2V617F ET.