AUTHOR=Muhammad Muhammad , Saifo Maher , Aljamali Majd , Alali Mousa , Ghanem Khaled M. 

TITLE=The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1334846

DOI=10.3389/fonc.2024.1334846

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>Polymorphisms in <italic>NUDT15</italic> may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the <italic>NUDT15</italic> (c.415C&gt;T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL).</p></sec><sec><title>Methods</title><p>This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The <italic>NUDT15</italic> genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated.</p></sec><sec><title>Results</title><p>A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with <italic>NUDT15</italic> (c.415C&gt;T; rs116855232) CT genotype, and 1 patient (1.08%) with <italic>NUDT15</italic> TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (<italic>P</italic>=0.009). Early onset leukopenia was significantly associated with the <italic>NUDT15</italic> polymorphism (OR: 6.16, 95% CI: 1.11-34.18, <italic>P</italic>=0.037). There was no association between the <italic>NUDT15</italic> genotype and hepatotoxicity.</p></sec><sec><title>Conclusion</title><p>Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in <italic>NUDT15</italic> rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the <italic>NUDT15</italic> genotype in pediatric patients with ALL.</p></sec>