Browsing by Author "Tükel, Ezgi Yağmur"

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Citation - WoS: 2
Citation - Scopus: 2
Identification of Potential Inhibitors for Drug Resistance in Acute Lymphoblastic Leukemia Through Differentially Expressed Gene Analysis and in Silico Screening
(Academic press inc elsevier science, 2024) Özay, Başak; Tükel, Ezgi Yağmur; Ayna Duran, Gizem; Kiraz, Yağmur
Acute lymphoblastic leukemia (ALL) is a disease of lymphocyte origin predominantly diagnosed in children. While its 5-year survival rate is high, resistance to chemotherapy drugs is still an obstacle. Our aim is to determine differentially expressed genes (DEGs) related to Asparaginase, Daunorubicin, Prednisolone, and Vincristine resistance and identify potential inhibitors via docking. Three datasets were accessed from the Gene Expression Omnibus database; GSE635, GSE19143, and GSE22529. The microarray data waes analyzed using R4.2.0 and Bioconductor packages, and pathway and protein-protein interaction analysis were performed. We identified 1294 upregulated DEGs, with 12 genes consistently upregulated in all four resistant groups. KEGG analysis revealed an association with the PI3K-Akt pathway. Among DEGs, 33 hub genes including MDM2 and USP7 were pinpointed. Within common genes, CLDN9 and HS3ST3A1 were subjected to molecular docking against 3556 molecules. Following ADMET analysis, three drugs emerged as potential inhibitors: Flunarizine, Talniflumate, and Eltrombopag. Molecular dynamics analysis for HS3ST3A1 indicated all candidates had the potential to overcome drug resistance, Eltrombopag displaying particularly promising results. This study promotes a further understanding of drug resistance in ALL, introducing novel genes for consideration in diagnostic screening. It also presents potential inhibitor candidates to tackle drug resistance through repurposing.
Citation - WoS: 4
Citation - Scopus: 4
Integrated Systems Biology Analysis of Acute Lymphoblastic Leukemia: Unveiling Molecular Signatures and Drug Repurposing Opportunities
(Springer, 2024) Budak, Betül; Tükel, Ezgi Yağmur; Turanlı, Beste; Kiraz, Yağmur
Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by aberrant proliferation and accumulation of lymphoid precursor cells within the bone marrow. The tyrosine kinase inhibitor (TKI), imatinib mesylate, has played a significant role in the treatment of Philadelphia chromosome-positive ALL (Ph + ALL). However, the achievement of durable and sustained therapeutic success remains a challenge due to the development of TKI resistance during the clinical course.The primary objective of this investigation is to propose a novel and efficacious treatment approach through drug repositioning, targeting ALL and its Ph + subtype by identifying and addressing differentially expressed genes (DEGs). This study involves a comprehensive analysis of transcriptome datasets pertaining to ALL and Ph + ALL in order to identify DEGs associated with the progression of these diseases to identify possible repurposable drugs that target identified hub proteins.The outcomes of this research have unveiled 698 disease-related DEGs for ALL and 100 for Ph + ALL. Furthermore, a subset of drugs, specifically glipizide for Ph + ALL, and maytansine and isoprenaline for ALL, have been identified as potential candidates for therapeutic intervention. Subsequently, cytotoxicity assessments were performed to confirm the in vitro cytotoxic effects of these selected drugs on both ALL and Ph + ALL cell lines.In conclusion, this study offers a promising avenue for the management of ALL and Ph + ALL through drug repurposed drugs. Further investigations are necessary to elucidate the mechanisms underlying cell death, and clinical trials are recommended to validate the promising results obtained through drug repositioning strategies.