Revisión bibliográfica sobre la influencia de polimorfismos genéticos en la vía del metotrexato en pacientes menores de 13 años con Leucemia Linfoblástica Aguda

Abstract

Methotrexate is an antimetabolite used in chemotherapy for acute lymphoblastic leukemia in underage patients, whose mechanism of action is the inhibition of DNA and RNA, decreasing blast cells. Genetic variability leads to the existence of polymorphisms in different genes, they are responsible for regulating transporters and enzymes, because of this, the drug response is different in each patient, in some cases it produces negative consequences and even death. The aim was to determine genetic polymorphisms in the methotrexate pathway for the treatment of acute lymphoblastic leukemia in patients under 13 years old, through a literature review, using articles reported since 2011 to 2021, in databases as PubMed, SciELO and Science Direct. The genes that reported toxicity were SLC19A1 rs1051266 G> A, MTHFR rs1801133 C> T, MTHFR rs1801131 A> C, TYMS rs151264360 D> I, SLCO1B1 rs4149056 T> C y rs4149081 G> A, DHFR rs442767 C> A, ABCC2 rs717620 C> T and ARID5B rs4948496 T> C. The adverse reactions mostly reported were leukopenia, neutropenia, hepatotoxicity, mucositis and lower MTX clearance. The most important polymorphisms were, rs1051266 G> A, rs1801133 C> T, rs1801131 A> C and rs4149056 T> C. Reduced clearance and hepatotoxicity are associated with these polymorphisms, mucositis (rs1051266), leukopenia (rs1801133) as well as neutropenia, myelotoxicity and neurotoxicity. In fact, we suggested more studies between these SNPs and adverse reactions, especially in the Latin American population.