Open AccessSignificance of TPMT and NUDT15 variants in 6-mercaptopurine metabolism in acute lymphoblastic leukaemia/lymphoma patients
Author(s) -
Ekaterina Kotova,
O A Gavrilina,
Andrey Sudarikov
Publication year - 2021
Publication title -
gematologiâ i transfuziologiâ
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.126
H-Index - 5
eISSN - 2411-3042
pISSN - 0234-5730
DOI - 10.35754/0234-5730-2021-66-2-253-262
Subject(s) - thiopurine methyltransferase , phenotype , drug metabolism , single nucleotide polymorphism , enzyme , gene , mercaptopurine , pharmacology , biology , drug , medicine , cancer research , genetics , genotype , biochemistry , azathioprine , disease
. Among main curative substances in acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is 6-mercaptopurine (6-MP). However, the severity of adverse reactions (ADRs) to this drug varies considerably among patients, which is sometimes conditioned by individual single nucleotide polymorphisms in key 6-MP metabolism enzyme genes. Aim — a literature review on the role of TPMT and NUDT15 gene variants in 6-MP metabolism in ALL/LBL. Main findings . The TPMT and NUDT15 genes encode enzymes mediating key steps of the 6-MP metabolism. The metabolites determine the 6-MP therapeutic and toxic properties, with ADRs emerging when their concentrations alter. A number of TPMT and NUDT15 single nucleotide polymorphisms are associated with varied activities of the encoded enzymes, and their allelic combinations condition functional and non-functional phenotypes. Non-functional variant carriers more likely develop toxicity on 6-MP treatment compared to functional phenotypes. Non-functional TPMT/NUDT15 carriers should have the 6-MP dosage reduced to minimise emerging ADRs.