@misc{10481/83439,
year = {2023},
month = {6},
url = {https://hdl.handle.net/10481/83439},
abstract = {Una paciente pediátrica de 6 años, diagnosticada de leucemia linfoblástica aguda (LLA) de riesgo intermedio, presenta milotoxicidad grave y múltiples infecciones durante la fase de inducción IB del tratamiento con 6-mercaptopurina (6-MP). En las siguientes fases del protocolo de tratamiento, que incluía también 6-MP, la paciente continúa 
mostrando aplasia de médula ósea y neutropenia, requiriendo numerosos ajustes de dosis e interrupciones. La dosis recomendada de 6-MP se reduce entonces al 5 %. El análisis farmacogenético, realizado en la fase de inducción 
IB, detectó tres polimorfismos de nucleótido único (SNPs) en el gen que codifica para la enzima tiopurina S-metiltransferasa (TPMT), observándose un fenotipo de metabolizador normal para esta enzima. Como consecuencia, se 
requirió de un segundo análisis farmacogenético más completo, que reveló polimorfismos patológicos en el gen de 
la hidrolasa Nudix 15 (NUDT15), explicaría la mielotoxicidad observada en esta paciente. Por ello, un análisis farmacogenético completo debería llevarse a cabo con anterioridad al inicio de 6-MP y de manera rutinaria en la práctica 
clínica, para conseguir prevenir los efectos adversos graves y/o el fracaso terapéutico.},
abstract = {A 6-year-old girl diagnosed with intermediate-risk acute lymphoblastic leukemia (ALL) presented with severe myelotoxicity and multiple infections during phase IB induction treatment with 6-mercaptopurine (6-MP). In the subsequent treatment phases, which included 6-MP, the patient continued to show bone marrow aplasia and neutropenia, necessitating numerous dose adjustments and interruptions. The recommended dose was eventually 
reduced to 5 %. A pharmacogenetic analysis, conducted in induction phase IB, detected three single-nucleotide 
polymorphisms (SNPs) of the thiopurine S-methyltransferase (TPMT) gene, and the phenotype of a normal metab olizer was observed. As a result of a second pharmacogenetic analysis, pathological polymorphisms were revealed 
in Nudix hydrolase 15 (NUDT15), which may explain the patient’s myelotoxicity. Hence, a pharmacogenetic analysis 
performed in advance would have been able to prevent her from suffering severe toxicity and/or treatment failure.},
organization = {Funding: The Virgen de las Nieves University Hospital Biobank was supported by grants co-funded by ERDF funds 
(EU) from the Instituto de Salud Carlos III (PT13/0010/0039).},
publisher = {Universidad de Granada, Facultad de Farmacia.},
keywords = {Farmacogenética},
keywords = {6-mercaptopurina},
keywords = {Leucemia linfoblástica aguda},
keywords = {Pharmacogenetics},
keywords = {6-mercaptopurine},
keywords = {Acute lymphoblastic leukemia},
title = {Impact of the homozygous mutation in Nudix hydrolase 15 on myelosuppression with 6-mercaptopurine in a European girl with acute lymphoblastic leukemia: A case report},
author = {Pineda-Lancheros, Laura Elena and Sánchez-Suárez, María del Mar and Marangoni-Iglecias, Luciana María and García-Fumero, Ricardo and Rojo-Tolosa, Susana and Moreno-Toro, Noelia},
}