Inherited Variants is a Genetic Determinant of Mercaptopurine/Methotrexate Intolerance in Children With Acute Lymphoblastic Leukemia

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dc.contributor.authorAtli, Emine Ikbal
dc.contributor.authorEker, Damla
dc.contributor.authorAtlı, Engin
dc.contributor.authorDemir, Selma
dc.contributor.authorYalçıntepe, Sinem
dc.contributor.authorGürkan, Hakan
dc.contributor.authorEren, Tuba
dc.date.accessioned2024-06-12T09:23:14Z
dc.date.available2024-06-12T09:23:14Z
dc.date.issued2022
dc.departmentTrakya Üniversitesien_US
dc.description.abstractObjectives: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children with distinctive features across its different subtypes. Although the etiology of ALL has not been fully elucidated, it has been shown that the onset of ALL is partly due to genetic factors. Genes related to drug transport, metabolism, detoxification and DNA repair could influence the cytotoxic effects associated with chemotherapy, including those involved in the transport (e.g., ABCB1, ABCC2, MTHFR and SLCO1B3), and transporter of folate (SLC19A1) of MTX and 6-MP. Likewise, genes involved in DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding (NR3C1) and DNA repair (TYMS) have previously been linked with cytotoxicity of 6-MP and/or MTX. Methods: In the current study, we therefore aimed to assess prior associations for 17 selected genetic variants in 5 genes, in a large cohort of 41 ALL patients treated with mercaptopurine (6-MP) and methotrexate (MTX) combination therapy or mono-therapy of whom detailed clinical toxicity datas were available. Results: Among the 17 variants in 5 genes evaluated according to the results of our study, the polymorphisms in rs2893881 (G/A) in ARID5B were closely related to therapy toxicity. To our knowledge, the effect of ARID5B variants on childhood ALL has not been studied in Turkey. Several genome-wide and candidate gene association studies have reported strong associations between ARID5B SNPs and risk of ALL and toxicity to therapeutic drugs in different populations. Conclusion: Finally, one of the most significant findings from this study is that ARID5B germline SNPs related to ALL treatment toxicity. To our knowledge, this is the first report to describe the relationship between ARID5B and ALL treatment response in the context of a preliminary ALL clinical trial. Further investigation of ARID5B variation in line with different ALL treatment regimens is required to improve its value as a prognostic marker.en_US
dc.identifier.doi10.14744/ejmi.2022.48878
dc.identifier.endpage442en_US
dc.identifier.issn2602-3164
dc.identifier.issue4en_US
dc.identifier.startpage436en_US
dc.identifier.trdizinid1133754en_US]
dc.identifier.urihttps://doi.org/10.14744/ejmi.2022.48878
dc.identifier.urihttps://search.trdizin.gov.tr/yayin/detay/1133754
dc.identifier.urihttps://hdl.handle.net/20.500.14551/12549
dc.identifier.volume6en_US
dc.indekslendigikaynakTR-Dizinen_US
dc.language.isoenen_US
dc.relation.ispartofEurasian Journal of Medical Investigationen_US
dc.relation.publicationcategoryMakale - Ulusal Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleInherited Variants is a Genetic Determinant of Mercaptopurine/Methotrexate Intolerance in Children With Acute Lymphoblastic Leukemiaen_US
dc.typeArticleen_US

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