Integrated systems biology analysis of acute lymphoblastic leukemia: unveiling molecular signatures and drug repurposing opportunities

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dc.contributor.authorBudak, Betul
dc.contributor.authorTukel, Ezgi Yagmur
dc.contributor.authorTuranli, Beste
dc.contributor.authorKiraz, Yagmur
dc.date.accessioned2026-04-04T18:55:21Z
dc.date.available2026-04-04T18:55:21Z
dc.date.issued2024
dc.departmentİstanbul Bilgi Üniversitesi
dc.description.abstractAcute 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.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [121Z765]; TUBITAK BIDEB 2210-A National MSc Scholarship Program
dc.description.sponsorshipThis work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) through project number 121Z765. The scholarship under the TUBITAK BIDEB 2210-A National MSc Scholarship Program provided to Betuel Budak is greatly acknowledged.
dc.identifier.doi10.1007/s00277-024-05821-w
dc.identifier.doi10.1007/s00277-024-05821-w
dc.identifier.endpage4134
dc.identifier.issn0939-5555
dc.identifier.issn1432-0584
dc.identifier.issue10
dc.identifier.pmid38836918
dc.identifier.scopus2-s2.0-85195174046
dc.identifier.scopusqualityQ2
dc.identifier.startpage4121
dc.identifier.urihttps://doi.org/10.1007/s00277-024-05821-w
dc.identifier.urihttps://hdl.handle.net/11411/10383
dc.identifier.volume103
dc.identifier.wosWOS:001242180900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofAnnals of Hematology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260402
dc.snmzKA_Scopus_20260402
dc.subjectAcute Lymphocytic Leukemia
dc.subjectPhiladelphia-Positive Acute Lymphoblastic Leukemia
dc.subjectBiomarkers
dc.subjectDrug Repositioning
dc.subjectSystems Biology
dc.titleIntegrated systems biology analysis of acute lymphoblastic leukemia: unveiling molecular signatures and drug repurposing opportunities
dc.typeArticle

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