The Frequency of Rs116855232 and Its Impact on Mercaptopurine-induced Toxicity in Syrian Children with Acute Lymphoblastic Leukemia

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Apr 2

PMID 38562167

Authors

Muhammad Muhammad

Maher Saifo

Majd Aljamali

Mousa Alali

Khaled M Ghanem

Affiliations

Soon will be listed here.

Abstract

Introduction: Polymorphisms in may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the (c.415C>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).

Methods: This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The 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.

Results: 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 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with 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 (=0.009). Early onset leukopenia was significantly associated with the polymorphism (OR: 6.16, 95% CI: 1.11-34.18, =0.037). There was no association between the genotype and hepatotoxicity.

Conclusion: Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the genotype in pediatric patients with ALL.

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