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Influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in childhood acute lymphoblastic leukemia [Elektronski vir]Erčulj, Nina ...The prediction of high-dose methotrexate (HD-MTX) toxicity is a key issue in the individualization of treatment in childhood acute lymphoblastic leukemia (ALL). Our aim was to evaluate the influence ... of MTX pathway polymorphisms on HD-MTX treatment outcome in children with ALL. In total, 167 children with ALLwere genotyped for methylenetetrahydrofolate dehydrogenase (MTHFD1) 1958G>A, methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C, and thymidylate synthase (TYMS) 2R>3R polymorphisms. MTHFD1 1958A allele significantly reduced odds of hepatotoxicity (adjusted P=0.009), while TYMS 3Rallele significantly reduced odds of leukocytopenia and thrombocytopenia (adjusted P=0.005 and adjusted P=0.002, respectively). MTHFR polymorphisms didnot influence HD-MTX-related toxicity, but a significant effect of MTHFR 677C>T-TYMS 2R>3R and MTHFD1 1958G>A-MTHFR 677C>T interactions on HD-MTX-related toxicity was observed. None of the investigated polymorphisms influenced survival. Our study suggests an important role of polymorphisms andgene-gene interactions within folate pathway in HD-MTX-related toxicity in childhood ALL.Vir: Leukemia & lymphoma. - ISSN 1026-8022 (Vol. 53, iss. 6, 2012, str. 1096-1104)Vrsta gradiva - e-članekLeto - 2012Jezik - angleškiCOBISS.SI-ID - 29379801
Avtor
Erčulj, Nina |
Faganel Kotnik, Barbara |
Debeljak, Maruša |
Jazbec, Janez, 1962- |
Dolžan, Vita
Teme
Leukemia, Lymphocytic, Acute |
Drug Therapy |
Methotrexate |
Therapeutic Use |
Toxicity |
Polymorphism (Genetics) |
Genotype |
Methylenetetrahydrofolate Dehydrogenase |
Child |
Thymidylate Synthetase |
Alleles |
Treatment Outcome |
Polimorfizem (genetika) |
Metilentetrahidrofolatna dehidrogenaza |
Metotreksat |
Genotip |
Levkemija limfocitna, akutna |
Otrok |
Zdravljenje, izid |
Aleli
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Erčulj, Nina | 30705 |
Faganel Kotnik, Barbara | 35916 |
Debeljak, Maruša | 15657 |
Jazbec, Janez, 1962- | 10972 |
Dolžan, Vita | 11711 |
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