NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia
Аутори
Ristivojević, BojanKotur, Nikola
Tošić, Nataša
Stanković, Biljana
Gašić, Vladimir
Pavlović, Đorđe
Jelovac, Marina
Milošević, Goran
Pavlović, Sonja
Zukić, Branka
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statisti...cal methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.
Кључне речи:
NUDT15 / 6-mercaptopurine / pharmacogene / acute lymphoblastic leukemiaИзвор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 81-81Издавач:
- Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Ristivojević, Bojan AU - Kotur, Nikola AU - Tošić, Nataša AU - Stanković, Biljana AU - Gašić, Vladimir AU - Pavlović, Đorđe AU - Jelovac, Marina AU - Milošević, Goran AU - Pavlović, Sonja AU - Zukić, Branka PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2128 AB - Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children with ALL of Serbian origin. Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association with surogate markers was assessed using adequate statistical methodology. Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C, NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159- 91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses (p=0.374)) of 6-mercaptopurine during the maintenance therapy. Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia. PB - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade C3 - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia T1 - NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia EP - 81 SP - 81 UR - https://hdl.handle.net/21.15107/rcub_imagine_2128 ER -
@conference{ author = "Ristivojević, Bojan and Kotur, Nikola and Tošić, Nataša and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Milošević, Goran and Pavlović, Sonja and Zukić, Branka", year = "2023", abstract = "Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children with ALL of Serbian origin. Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association with surogate markers was assessed using adequate statistical methodology. Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C, NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159- 91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses (p=0.374)) of 6-mercaptopurine during the maintenance therapy. Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.", publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade", journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia", title = "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia", pages = "81-81", url = "https://hdl.handle.net/21.15107/rcub_imagine_2128" }
Ristivojević, B., Kotur, N., Tošić, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Milošević, G., Pavlović, S.,& Zukić, B.. (2023). NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 81-81. https://hdl.handle.net/21.15107/rcub_imagine_2128
Ristivojević B, Kotur N, Tošić N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Milošević G, Pavlović S, Zukić B. NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:81-81. https://hdl.handle.net/21.15107/rcub_imagine_2128 .
Ristivojević, Bojan, Kotur, Nikola, Tošić, Nataša, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Milošević, Goran, Pavlović, Sonja, Zukić, Branka, "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):81-81, https://hdl.handle.net/21.15107/rcub_imagine_2128 .