Pharmacogenomics · 2025
Pharmacogenetic markers of PEG-asparaginase toxicity in Brazilian pediatric ALL: insights from a multicenter prospective cohort study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Cecconello Daiane Keller, de Souza Silva Klerize Anecely, de Senna Evelin Cristine Mendonça, Carlotto Lucas Alfeu, de Souza Amanda Másculo, Lins Mecneide Mendes, Magalhães Isis Maria Quezado Soares, de Sousa Ana Virgínia Lopes, Epelman Sidnei, Cristofani Lilian, Barros Tais Tereziano, Pianovski Mara, Moreira Larissa Polis, Rechenmacher Ciliana, Daudt Liane Esteves, Michalowski Mariana Bohns
Аннотация
AIMS: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Although PEG-asparaginase (PEG-ASNase) is a key drug in treatment, hypersensitivity reactions, pancreatitis, and silent inactivation remain major challenges. Interindividual genetic variability influences drug metabolism and toxicity, and pharmacogenetic research aims to identify these variants early to predict specific responses effectively.
METHODS: We investigated the association between variants in NFATC2, GRIA1, CNOT3, MYBBP1A, ARHGAP28, ULK2, and RGS6 and PEG-ASNase - induced toxicities in a prospective multicenter study of 441 children with ALL. Genotyping was performed using TaqMan probes on saliva-extracted DNA.
RESULTS: Among patients, 9.7% developed allergies, 3.4% pancreatitis, and 10.1% silent inactivation, which was significantly associated with allergic reactions (p < 0.05). No significant associations were found between the genetic variants and hypersensitivity or pancreatitis (p > 0.05).
CONCLUSIONS: No statistically significant associations were observed between the selected variants and PEG-ASNase-related hypersensitivity or pancreatitis in this cohort.This study highlights the importance of ancestry-informed approaches in pharmacogenomic research for ALL.
METHODS: We investigated the association between variants in NFATC2, GRIA1, CNOT3, MYBBP1A, ARHGAP28, ULK2, and RGS6 and PEG-ASNase - induced toxicities in a prospective multicenter study of 441 children with ALL. Genotyping was performed using TaqMan probes on saliva-extracted DNA.
RESULTS: Among patients, 9.7% developed allergies, 3.4% pancreatitis, and 10.1% silent inactivation, which was significantly associated with allergic reactions (p < 0.05). No significant associations were found between the genetic variants and hypersensitivity or pancreatitis (p > 0.05).
CONCLUSIONS: No statistically significant associations were observed between the selected variants and PEG-ASNase-related hypersensitivity or pancreatitis in this cohort.This study highlights the importance of ancestry-informed approaches in pharmacogenomic research for ALL.