Chromosomal translocations and genetic polymorphisms of folate enzymes and methotrexate transporters as possible predictors of toxicity in children with acute lymphoblastic leukemia

Metotrexate (MTX), was the first drug used to induce remissions in children with acute lymphoblastic leukemia (LLA), since 1948. Intravenous MTX infusion at high doses (= 0.5 g/m2), in the consolidation phase in combination with other chemotherapeutic agents, significantly improves the result in patients of intermediate and high risk. MTX pharmacokinetics is related to its efficacy and toxicity, so the high plasma levels of the drug, are associated with a high adverse effect risk. Chemotherapy toxicity is a common cause of morbidity and mortality in children with lla and long -term sequelae. It has been suggested that the function and/or expression of the enzymes and transporters that participate in the MTX pathway can be altered by genetic polymorphisms and chromosomal translocations; Which substantially influence pharmacokinetics and response to treatment with high dose MTX. Objective: Finding predictors of toxicity due to metretrexate in children = 18 years with lla through the evaluation of chromosomal translocations and genetic polymorphisms of the enzymes involved in the metabolic pathway of folate and MTX transporters. Methodology: A study will be carried out that will include patients = 18 years diagnosed with lla and treated at the Solca-Loja, Cuenca and Manabí hospital, which are in the consolidation phase, between February 1 and August 31, 2017. The translocations T (9,22) will be analyzed that includes the P190 and P210 and depending on the cutting point of the chromosome chromosome point (PH), T (4,11), T (1,19), and T (12,21) by conventional cytogenetics. While by real -time PCR, the following polymorphisms will be identified: SLCO1B1, MTHFF C677T, MTHFF A1298C., ABCB1 C1236T. The data will be analyzed by the SPSS V21 statistical program and by SNPSTATs. Results: This work aims to identify possible markers predictors of MTX toxicity, which could contribute to the development of the individualization of treatment with that drug, in particular, for the children's lla.

15th UNIVERSITY RESEARCH COMPETITION