Journal of Advances in Medical and Biomedical Research

en Assessment of TPMT Gene Polymorphisms and its Enzyme Activity in Pediatric Acute Lymphoblastic Leukemia Patients Receiving 6-Mercaptopurine: Correlation with Myelosuppression and Hepatotoxicity Medical Biology Medical Biology مقاله پژوهشی Original Research Article Background and Objective: The TPMT enzyme is pivotal for the metabolism and inactivation of thiopurine drugs such as 6-mercaptopurine (6-MP). Genetic variations in TPMT can alter enzyme activity, leading to drug toxicity. This study aimed to evaluate common TPMT gene polymorphisms, measure plasma enzyme levels, and investigate their association with 6-MP-induced myelosuppression and hepatotoxicity in ALL patients. Patients and Methods: A cohort of 98 ALL patients on 6-MP maintenance therapy was analyzed. Common TPMT variants (*2, *3B, *3C, 3A) were genotyped using PCR-RFLP and allele-specific PCR, with confirmatory sequencing in selected samples. Plasma TPMT levels were measured in 70 patients via ELISA. Correlations between genotype, enzyme activity, and adverse effects (neutropenia, leukopenia, hepatotoxicity) were assessed statistically. Results: The TPMT*3B allele was identified at a low frequency (0.71%), with one heterozygous case (1.1%). No other variants were detected. Plasma analysis revealed 11.4% of patients had low enzyme activity, yet this was not associated with common TPMT genotypes (P=1.0). However, low enzyme activity showed a significant correlation with myelosuppression—leukopenia (P=0.04) and neutropenia (P=0.02)—but not with hepatotoxicity (P=0.12). Conclusion: Low plasma TPMT enzyme activity, not the common genetic polymorphisms, is significantly linked to myelosuppression in ALL patients receiving 6-MP. These results suggest that direct enzyme activity measurement, alongside genetic screening, may help predict and mitigate adverse hematological effects during thiopurine therapy.   Acute Lymphoblastic Leukemia, Thiopurine Methyltransferase, Polymorphism, Pharmacogenetics, 6-Mercaptopurine, Leukopenia 13 13 http://journal.zums.ac.ir/browse.php?a_code=A-10-7480-1&slc_lang=en&sid=1 Saghar Zakeri Saghar.za@gmail.com 5200319475328460090169 5200319475328460090169 No Department of Medical and Molecular Genetics, Nobel Pathobiology and Genetics Laboratory, Isfahan, Iran Maryam Jafarian jfryanmaryam@gmail.com 5200319475328460090170 5200319475328460090170 No Department of Molecular Medicine and Genetics, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Samin Alavi saminalavi@hotmail.com 5200319475328460090171 5200319475328460090171 No Pediatric Conjenital Hematologic Disorders Research Center, Research Institute of Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Shahla Rahmani Shahlarahmani7075@gmail.com 5200319475328460090172 5200319475328460090172 No Department of Medical Laboratory Sciences, School of Allied Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran Yousef Mortazavi yousef1mortazavi@gmail.com 5200319475328460090173 5200319475328460090173 Yes Department of Molecular Medicine and Genetics, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran