جمعه 13 شهریور 1405
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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.
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.
فهرست منابع
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