Thiopurine S-Methyltransferase Genotyping in Iraqi Childhood Acute Lymphoblastic Leukemia Patients ; A Single Institute Study

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer seen in childrenworldwide and is the most common cancer in children under 14 years of age. Although there havebeen major advances in treatment approaches for childhood ALL, serious toxicities such as profoundleukopenia frequently affect treatment and lead to life threatening consequences such as severeinfections and even death. There has been a lot of interest in inter-individual differences in drugmetabolizing enzymes in order to better adjust drug dosage and therapy. In this regards, ThiopurineS-Methyltransferase (TMPT) was the first pharmacogene that showed a substantial associationwith Mercaptopurine (6-MP) maximum tolerated dose and 6-MP related toxicities leading to theimplementation of TPMT genotyping before drug administration Aim: To identify the most commonTPMT polymorphism (TPMT*3A, TPMT*3B and TPMT*3C) and its frequencies in a sample of IraqiALL paediatric patients. Methods: A cross sectional study was performed for 79 patients with Acutelymphoblastic leukemia . Genotyping for (*3A , *3B , *3C ) the TPMT gene was performed by theallele-specific multiplex-PCR analysis method. Results: The TPMT*3A mutant allele was found in 18patients with allele frequency of (22.8 %), while TPMT*3C mutant allele was detected in 5 childrenwith allele frequency of 6.3% . But TPMT*3B mutant allele was not detected in whole sample ALLpatients .The correlation between gender and the polymorphism was not statically significant as p-value0.23.. Conclusion: TMPT genotyping is an essential tool to reduce the cytotoxic effects of the anticancerdrug 6-MP in Iraqi paediatric patients with ALL .