ITPA, TPMT, and NUDT15 Genetic Polymorphisms Predict 6-Mercaptopurine Toxicity in Middle Eastern Children With Acute Lymphoblastic Leukemia.

摘要: Background: Acute lymphoblastic leukemia (ALL) is the most common cancer seen in children worldwide and Middle East. Although there have been major advances treatment approaches for childhood ALL, serious toxicities do occur but with significant inter-individual variability. The aim of this study to measure frequency polymorphisms candidate genes involved 6-Mercaptopurine (6-MP) disposition a combined cohort Eastern Children evaluate whether these predict 6-MP intolerance toxicity during ALL maintenance therapy. Methods: includes treated on two protocols from cohorts; one Lebanon (N = 136) another Kurdistan province Iran 74). Genotyping following six genetic polymorphisms: ITPA 94C > A (rs1127354) IVS2+21A C (rs7270101), TPMT*2 238G (rs1800462), TPMT*3B 460G (rs1800460) *3C 719A G (rs1142345), NUDT15 415C T (rs116855232) was performed analyzed association dose intensity toxicity. Results: As expected, TPMT variants were uncommon. ITPA, both more Lebanese as compared Kurdish minor allele 0.05 0.14 only 121), 0.01 either polymorphism Kurds. toxic effects depicted median 33.33%, followed by 46.65% TPMT*3A polymorphism, 65.33% risk carriers 74% carriers, comparison 100% homozygous wild type (P < 0.001). In addition, onset febrile neutropenia significantly higher variant cohorts. Conclusions: These data confirm predictive role TPMT, NUDT15, ALL. Given relatively high our their intensity, we recommend that physicians consider genotyping conjunction prior therapy children.