Optimizing mercaptopurine therapy in indian pediatric ALL: The role of TPMT and NUDT15 genetic polymorphisms

This review aims to present and assess the existing scientific evidence on various genetic mutations of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) and their potential implications in mercaptopurine (MP) intolerance among Indian ethnic patients with acute lymphoblastic leukemia (ALL). The objective is to enhance monitoring approaches for MP therapy to optimize therapeutic outcomes and minimize adverse effects or toxicity in pediatric ALL patients.

An extensive search was conducted, and data revealing the genetic alterations of TPMT and NUDT15 on MP dosing in ALL patients was obtained using PubMed, Google Scholar, and clinicaltrials.gov.

ALL constitutes approximately 30% of malignancies in children. The utilization of MP, a thiopurine drug, is widespread in ALL treatment. Nonetheless, the common adverse reactions such as myelosuppression, leucopenia, and hepatotoxicity restrict their usage. This review indicates that NUDT15 variations are more prevalent than TPMT among Indian patients, serving as a potential indicator for myelosuppression and leukopenia resulting from MP. Consequently, the genotyping of TPMT and NUDT15 before MP treatment may assist in determining the appropriate dosage of MP to prevent life-threatening infections. It is important to acknowledge that numerous factors can influence the variability in response to medications. Other variables that may impact the ability to predict a phenotype based on genotype include environmental and endogenous elements such as comorbidities, concurrent medications, renal function, and hepatic function. Non-genetic elements should be considered within the specific clinical context of an individual patient when implementing recommended dosage adjustments.

This evaluation indicates that NUDT15 variations are more prevalent than TPMT among Indian patients. Consequently, the genotyping of TPMT and NUDT15 before MP treatment may assist in determining the appropriate dosage of MP to prevent life-threatening infections.