The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia
Аутори
Ristivojević, BojanKotur, Nikola
Stanković, Biljana
Gašić, Vladimir
Pavlović, Đorđe
Jelovac, Marina
Pavlović, Sonja
Zukić, Branka
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute
lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase,
inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal
transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was
to determine if the selected genetic variants are associated with the development of VIPN in ALL
children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic
markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect
variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117
(rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their
association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17
pharmacogenes fr...om in-house next-generation sequencing data was also done. Data on allele frequency
distribution for European population were extracted from public databases. During the treatment,
17.86% of patients developed VIPN. Association analyses have shown that none of the investigated
genetic variants contributed to the occurrence of VIPN in our study group. Population
pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN.
Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More
comprehensive approaches are needed to identify panel of genes that could explain the VIPN
development after VCR administration in ALL patients. Utilizing better designed GWAS studies and
more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive
tests of VIPN to individualize therapy for ALL in children.
Кључне речи:
vincristine / vincristine-induced peripheral neuropathy / pediatric acute lymphoblastic leukemia / pharmacogenetics / CYP3А5 / CEP72 / ACTG1 / MIR3117 / MIR4481Извор:
Genetics & Applications, 2023, 7, 2 (Special edition), 109-Издавач:
- Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
Напомена:
- Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina - ABMBBIH May, 2023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Ristivojević, Bojan AU - Kotur, Nikola AU - Stanković, Biljana AU - Gašić, Vladimir AU - Pavlović, Đorđe AU - Jelovac, Marina AU - Pavlović, Sonja AU - Zukić, Branka PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1902 AB - Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was to determine if the selected genetic variants are associated with the development of VIPN in ALL children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117 (rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for European population were extracted from public databases. During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the investigated genetic variants contributed to the occurrence of VIPN in our study group. Population pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More comprehensive approaches are needed to identify panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed GWAS studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children. PB - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo C3 - Genetics & Applications T1 - The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia IS - 2 (Special edition) SP - 109 VL - 7 UR - https://hdl.handle.net/21.15107/rcub_imagine_1902 ER -
@conference{ author = "Ristivojević, Bojan and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Pavlović, Sonja and Zukić, Branka", year = "2023", abstract = "Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was to determine if the selected genetic variants are associated with the development of VIPN in ALL children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117 (rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for European population were extracted from public databases. During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the investigated genetic variants contributed to the occurrence of VIPN in our study group. Population pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More comprehensive approaches are needed to identify panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed GWAS studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.", publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo", journal = "Genetics & Applications", title = "The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia", number = "2 (Special edition)", pages = "109", volume = "7", url = "https://hdl.handle.net/21.15107/rcub_imagine_1902" }
Ristivojević, B., Kotur, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Pavlović, S.,& Zukić, B.. (2023). The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia. in Genetics & Applications Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7(2 (Special edition)), 109. https://hdl.handle.net/21.15107/rcub_imagine_1902
Ristivojević B, Kotur N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Pavlović S, Zukić B. The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia. in Genetics & Applications. 2023;7(2 (Special edition)):109. https://hdl.handle.net/21.15107/rcub_imagine_1902 .
Ristivojević, Bojan, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Pavlović, Sonja, Zukić, Branka, "The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia" in Genetics & Applications, 7, no. 2 (Special edition) (2023):109, https://hdl.handle.net/21.15107/rcub_imagine_1902 .