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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-članek
    Leto - 2012
    Jezik - angleški
    COBISS.SI-ID - 29379801

    Povezava(-e):

    http://informahealthcare.com/doi/abs/10.3109/10428194.2011.639880
    DOI

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