@article{Lazić_Kotur_Krstovski_Dokmanović_Zukić_Predojević-Samardžić_Životić_Miločević_Đorić_Janić_Pavlović_2017, title={Importance of pharmacogenetic markers in the methylenetetrahydrofolate reductase gene during methotrexate treatment in pediatric patients with acute lymphoblastic leukemia}, volume={69}, url={https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/268}, abstractNote={<p>Despite remarkable progress in survival of children with acute lymphoblastic leukemia (ALL) which has reached about 85%, early toxicity and relapse rate remain issues that need to to be resolved. Genetic variants are important factors influencing the metabolism of cytotoxic drugs in ALL treatment. Variants in genes coding for methotrexate (MTX)-metabolizing enzymes are under constant scientific interest due to their potential impact on drug toxicity and relapse rate. We investigated methylenetetrahydrofolate reductase (<em>MTHFR)</em> c.677C>T and <em>MTHFR </em>c.1298A>C variants as pharmacogenetic markers of MTX toxicity and predictors of relapse. The study enrolled 161 children with ALL, treated according to the current International Berlin-Frankfurt-Munster group (BFM) for diagnostics and treatment of leukemia and lymphoma protocols. Genotyping was performed using PCR-RFLP and allele-specific PCR assays. Our results revealed similar distributions of <em>MTHFR </em>c.677C>T and <em>MTHFR </em>c.1298A>C genotypes among 104 healthy individuals as compared to pediatric ALL patients. A lower incidence of early MTX toxicity was noted in the <em>MTHFR</em> c.677TT genotype (p=0.017), while <em>MTHFR </em>c.1298A>C genotypes were not associated with MTX toxicity. Carriers of any <em>MTHFR </em>c.677C>T and <em>MTHFR </em>c.1298A>C genotypes did not experience decreased overall survival (OAS) or higher relapse rates. Genetic variants in the <em>MTHFR </em>gene are not involved in leukemogenesis in pediatric ALL. The presence of the <em>MTHFR </em>c.677TT genotype was recognized as a predictive factor for decreased MTX toxicity during the intensification phase of therapy. Neither <em>MTHFR </em>c.677C>T nor <em>MTHFR </em>c.1298A>C genotypes correlated with an increased number of toxic deaths or relapse rate. Our study emphasizes the importance of implementing pharmacogenetic markers in order to optimize pediatric ALL therapy.</p><p><a href="https://doi.org/10.2298/ABS160325091L">https://doi.org/10.2298/ABS160325091L</a></p><div><p><strong>Received:</strong> March 25, 2016; <strong>Revised:</strong> April 12, 2016; <strong>Accepted:</strong> April 12, 2016; <strong>Published online:</strong> October 4, 2016</p><p><strong>How to cite this article:</strong> Lazić J, Kotur N, Krstovski N, Dokmanović L, Zukić B, Predojević-Samardžić J, Životić M, Milošević G, Đorić M, Janić D, Pavlović S. Importance of pharmacogenetic markers in the methylenetetrahydrofolate reductase gene during methotrexate treatment in pediatric patients with acute lymphoblastic leukemia. Arch Biol Sci. 2017;69(2):239-46.</p></div>}, number={2}, journal={Archives of Biological Sciences}, author={Lazić, Jelena and Kotur, Nikola and Krstovski, Nada and Dokmanović, Lidija and Zukić, Branka and Predojević-Samardžić, Jelica and Životić, Maja and Miločević, Goran and Đorić, Milica and Janić, Dragana and Pavlović, Sonja}, year={2017}, month={May}, pages={239–246} }