Polimorfismos del gen tiopurina S-metiltransferasa (TPMT) en pacientes pediátricos peruanos con leucemia linfoblástica aguda

Objective: To identify the allelic and genotypic frequencies, as well as the probable phenotypes, of thiopurine S-methyltransferase (TPMT) gene variants in a cohort of pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) treated in the hematology department of a pediatric tertiary care institute. Materials and methods: A descriptive cross-sectional study was conducted. Peripheral blood samples were analyzed to detect the polymorphisms rs1800460, rs1142345, and rs1800462 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR (ASPCR) techniques. The study population included 112 unrelated pediatric patients who provided signed informed consent and/or assent, as appropriate. Biological samples showing evidence of coagulation and/or contamination were excluded. Allele and genotype frequencies were calculated, the probable TPMT phenotypes were inferred, and statistical analyses of the results were performed. Results: The allele frequencies observed were as follows: TPMT*1 (82.14 %), TPMT*2 (8.93 %), TPMT*3A (0.45 %), and TPMT*3B (8.48 %). The TPMT*3C variant was not detected. The following genotypes were identified: TPMT*1/TPMT*1 (wild-type homozygote) in 64.29 % of patients, TPMT*1/TPMT*2 in 17.86 %, TPMT*1/TPMT*3B in 16.96 %, and TPMT*1/TPMT*3A in 0.89 %. Based on these genotypes, the inferred phenotypes corresponded to normal enzymatic activity in 64.29 % of patients and intermediate activity in 35.71 %. No genotypes associated with low or absent TPMT activity were identified. Conclusions: TPMT genotyping in pediatric patients with B-ALL revealed that TPMT*1 was the most prevalent, followed by the TPMT*2, TPMT*3B, and TPMT*3A variants. Additionally, a high frequency of phenotypes with intermediate predicted enzymatic activity was identified. These results underscore the need for further studies exploring TPMT genotype–phenotype correlations and support the relevance of TPMT genotyping as a tool to personalize thiopurine therapy, aiming to enhance treatment efficacy while minimizing the risk of adverse reactions or toxicity.