Introduction: Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. This study aimed to the analysis of relative expression of gene FMS-like receptor tyrosine kinase-3 (FLT3) in AML. FLT3 is a member of the class III RTK (receptor tyrosine kinase progenitor cells). Its expression in these cells means that FLT3 has an important role in the pathogenesis of AML. FLT3 mutations commonly co-occur with mutations such as cytogenetically normal AML and likely modulate prognostic impact. the prognostic impact of FLT3 mutation is still up for debate.
Methods: Gene expression data of AML patients (GSE114868) was obtained from the NCBI Gene
Expression Omnibus (GEO) and a gene named FLT3 was selected for further study. Then FLT3 was analyzed by GEPIA2 to find differentially expressed genes. GEPIA2 database was used to support the possibility of a correlation between FLT3 and Acute myeloid leukemia, and it evaluated the correlation between the gene and patient survival. Through ENRICHR, KEGG, REACTOME databases, and Gene Cards, gene ontology information and biological pathway and Molecular function involvement were processed. miRNA SNP, dbSNP, SIFT, and UniProt were used to calculate the probability of each single nucleotide polymorphism (SNP) and Mutation based on the quality of the base assignments and the curves in the chromatogram files. Also, HOPE was used to analyze the impacts of point mutations on the structure and function carried out by a protein. STRING and miRWalk were utilized to find significant Protein and miRNA interactions with FLT3 mRNA in the 3’UTR region. Additionally, the selected miRNA was searched in LncRRIsearch and LncBase v.3 to find strong interactions with LncRNAs and construct a predictive ceRNA network.
Results: Based on analysis of the GEO dataset, The expression of FLT3 was shown increasingly (|logFC| = 6.71399118, adj. P value = 4.15E-40) in AML samples. Through ENRICHR, KEGG, and REACTOME pathways, FLT3 plays a special role in Acute myeloid leukemia and it is a part of different molecular functions and biological processes such as lymphoid progenitor cell differentiation. Analysis of miRNA SNP, dbSNP, SIFT, and UniProt showed FLT3 mutations likely modulate prognostic impact. Based on String, the interaction of FLT3 has been shown with different proteins such as FLT3LG, GRB2, HSP90AA1, HRAS, NRAS, PTPN11, KRAS, PIK3R1, KITLG. Analysis of possible miRNA-mRNA interactions in miRNAWALK revealed hsa-miR-2115-5p (energy= -21.1) as a significant interactor to FLT3 mRNA. This miRNA was then searched in LncRRIsearch and LncBase v.3, and it had the strongest interactions with HELPAR (energy= -103.73), LINCO1215 (energy= -77.19), HCG18.
Conclusion: In conclusion, FMS-like receptor tyrosine kinase-3 (FLT3) is overexpressed in AML based on Analysis of different databases and forms a possible lncRNA and ceRNA network among hsa-miR-2115-5p, HELLPAR, LINCO1215, HCG18.