Influence of variants in folate metabolism genes on 6-mercaptopurine induced toxicity during treatment for childhood acute lymphocytic leukemia
Нема приказа
Аутори
Milosević, GoranKotur, Nikola
Lazić, Jelena
Krstovski, Nada
Stanković, Biljana
Zukić, Branka
Janić, Dragana
Jurisić, Vladimir
Pavlović, Sonja
Dokmanović, Lidija
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Purpose: To analyze influence of variants in TYMS, MTHFR, SLC19A1 and DHFR genes on 6-mercaptopurine (MP) induced toxicity during maintenance phase of treatment for childhood acute lymphocytic leukemia (ALL). Methods: One-hundred twenty-seven children with ALL that received maintenance therapy were involved in this study. All patients were treated according to Berlin-Frankfurt-Muenster (BFM) based protocols. Myelotoxicity and hepatotoxicity were evaluated using surrogate markers (median 6-MP dose, number of leukopenic episodes and levels of bilirubin and transaminases on each visit). Results: Higher number of leukopenic episodes, as a surrogate marker of 6-MP myelotoxicity, was found in carriers of TYMS 3R3R and 3R4R genotypes (p=0.067) as well as in TYMS 3R6bp+ (28bp VNTR, 6bp indel) haplotype carriers (p=0.015). Carriers of DHFR CATAG (-680, -675, -556, -464, -317) haplotype were also found to have higher number of leukopenic episodes (p=0.070). SLC19A1 c.80A allele (p=0.079) and TYM...S 2R6bp+ (5'UTR VNTR, 6bp indel) haplotype carriers (p=0.078) had fewer leukopenic episodes. No difference in genotype frequencies between the control group of volunteered blood donors and childhood ALL patients was found. Conclusions: Variants in TYMS, SLC19A1 and DHFR genes are potential biomarkers of myelotoxicity and could be used for 6-MP therapy individualization in maintenance phase of childhood ALL treatment, alongside with well-established TPMT variants.
Кључне речи:
TYMS / SLC19A1 / MTHFR / DHFR / acute lymphoblastic leukemia / 6-mercaptopurine myelotoxicityИзвор:
Journal of Buon, 2019, 24, 5, 2075-2083Издавач:
- Balkan Union of Oncology (B.U.ON.)
Финансирање / пројекти:
- Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Milosević, Goran AU - Kotur, Nikola AU - Lazić, Jelena AU - Krstovski, Nada AU - Stanković, Biljana AU - Zukić, Branka AU - Janić, Dragana AU - Jurisić, Vladimir AU - Pavlović, Sonja AU - Dokmanović, Lidija PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1235 AB - Purpose: To analyze influence of variants in TYMS, MTHFR, SLC19A1 and DHFR genes on 6-mercaptopurine (MP) induced toxicity during maintenance phase of treatment for childhood acute lymphocytic leukemia (ALL). Methods: One-hundred twenty-seven children with ALL that received maintenance therapy were involved in this study. All patients were treated according to Berlin-Frankfurt-Muenster (BFM) based protocols. Myelotoxicity and hepatotoxicity were evaluated using surrogate markers (median 6-MP dose, number of leukopenic episodes and levels of bilirubin and transaminases on each visit). Results: Higher number of leukopenic episodes, as a surrogate marker of 6-MP myelotoxicity, was found in carriers of TYMS 3R3R and 3R4R genotypes (p=0.067) as well as in TYMS 3R6bp+ (28bp VNTR, 6bp indel) haplotype carriers (p=0.015). Carriers of DHFR CATAG (-680, -675, -556, -464, -317) haplotype were also found to have higher number of leukopenic episodes (p=0.070). SLC19A1 c.80A allele (p=0.079) and TYMS 2R6bp+ (5'UTR VNTR, 6bp indel) haplotype carriers (p=0.078) had fewer leukopenic episodes. No difference in genotype frequencies between the control group of volunteered blood donors and childhood ALL patients was found. Conclusions: Variants in TYMS, SLC19A1 and DHFR genes are potential biomarkers of myelotoxicity and could be used for 6-MP therapy individualization in maintenance phase of childhood ALL treatment, alongside with well-established TPMT variants. PB - Balkan Union of Oncology (B.U.ON.) T2 - Journal of Buon T1 - Influence of variants in folate metabolism genes on 6-mercaptopurine induced toxicity during treatment for childhood acute lymphocytic leukemia EP - 2083 IS - 5 SP - 2075 VL - 24 UR - https://hdl.handle.net/21.15107/rcub_imagine_1235 ER -
@article{ author = "Milosević, Goran and Kotur, Nikola and Lazić, Jelena and Krstovski, Nada and Stanković, Biljana and Zukić, Branka and Janić, Dragana and Jurisić, Vladimir and Pavlović, Sonja and Dokmanović, Lidija", year = "2019", abstract = "Purpose: To analyze influence of variants in TYMS, MTHFR, SLC19A1 and DHFR genes on 6-mercaptopurine (MP) induced toxicity during maintenance phase of treatment for childhood acute lymphocytic leukemia (ALL). Methods: One-hundred twenty-seven children with ALL that received maintenance therapy were involved in this study. All patients were treated according to Berlin-Frankfurt-Muenster (BFM) based protocols. Myelotoxicity and hepatotoxicity were evaluated using surrogate markers (median 6-MP dose, number of leukopenic episodes and levels of bilirubin and transaminases on each visit). Results: Higher number of leukopenic episodes, as a surrogate marker of 6-MP myelotoxicity, was found in carriers of TYMS 3R3R and 3R4R genotypes (p=0.067) as well as in TYMS 3R6bp+ (28bp VNTR, 6bp indel) haplotype carriers (p=0.015). Carriers of DHFR CATAG (-680, -675, -556, -464, -317) haplotype were also found to have higher number of leukopenic episodes (p=0.070). SLC19A1 c.80A allele (p=0.079) and TYMS 2R6bp+ (5'UTR VNTR, 6bp indel) haplotype carriers (p=0.078) had fewer leukopenic episodes. No difference in genotype frequencies between the control group of volunteered blood donors and childhood ALL patients was found. Conclusions: Variants in TYMS, SLC19A1 and DHFR genes are potential biomarkers of myelotoxicity and could be used for 6-MP therapy individualization in maintenance phase of childhood ALL treatment, alongside with well-established TPMT variants.", publisher = "Balkan Union of Oncology (B.U.ON.)", journal = "Journal of Buon", title = "Influence of variants in folate metabolism genes on 6-mercaptopurine induced toxicity during treatment for childhood acute lymphocytic leukemia", pages = "2083-2075", number = "5", volume = "24", url = "https://hdl.handle.net/21.15107/rcub_imagine_1235" }
Milosević, G., Kotur, N., Lazić, J., Krstovski, N., Stanković, B., Zukić, B., Janić, D., Jurisić, V., Pavlović, S.,& Dokmanović, L.. (2019). Influence of variants in folate metabolism genes on 6-mercaptopurine induced toxicity during treatment for childhood acute lymphocytic leukemia. in Journal of Buon Balkan Union of Oncology (B.U.ON.)., 24(5), 2075-2083. https://hdl.handle.net/21.15107/rcub_imagine_1235
Milosević G, Kotur N, Lazić J, Krstovski N, Stanković B, Zukić B, Janić D, Jurisić V, Pavlović S, Dokmanović L. Influence of variants in folate metabolism genes on 6-mercaptopurine induced toxicity during treatment for childhood acute lymphocytic leukemia. in Journal of Buon. 2019;24(5):2075-2083. https://hdl.handle.net/21.15107/rcub_imagine_1235 .
Milosević, Goran, Kotur, Nikola, Lazić, Jelena, Krstovski, Nada, Stanković, Biljana, Zukić, Branka, Janić, Dragana, Jurisić, Vladimir, Pavlović, Sonja, Dokmanović, Lidija, "Influence of variants in folate metabolism genes on 6-mercaptopurine induced toxicity during treatment for childhood acute lymphocytic leukemia" in Journal of Buon, 24, no. 5 (2019):2075-2083, https://hdl.handle.net/21.15107/rcub_imagine_1235 .