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|Title||Thiopurine Methyltransferase Genotyping in Childhood Acute Lymphoblastic Leukemia Patients in Gaza Strip|
Background: The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Three common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT*2 (238G>C), TPMT*3A (460G>A, 719A>G) and TPMT*3C (719A>G). Objective: The aim of the present study was to determine the frequency of the functional TPMT polymorphisms and their association with the occurrence of adverse events, during 6-mercaptopurine therapy in pediatric acute lymphoblastic leukemic (ALL) patients in Gaza Strip. Methods:A total of 56 DNA samples from all pediatric ALL patients admitted to the pediatric hematology departments of Gazastrip hospitals were analyzed. Genomic DNA from peripheral blood leukocytes was isolated and the TPMT*2, TPMT*3A and TPMT*3C allelic polymorphism was determined by PCR- RFLP and allele specific PCR technique. Results: No TPMT*2, *3C mutant alleles were detected. Only the TPMT*3A allele was detected in one patient out of 56 DNA samples of pediatric ALL patients inGazastrip. Thus, frequency of TPMT*3A allele was 0.89%. Fourteen patients of ALL were suffering from mylotoxicity during 6MP therapy. From our results, no significant association could be established between clinical and laboratory data and/or the presence of the mutation in TPMT gene. The calculated incidence of ALL in children in Gaza Strip is 2 cases per 100000 children. The incidence of ALL is higher in males than in females. The mean age of ALL incidences in Gaza Strip is 4.4 ± 2.6 years. Conclusion: This is the first analysis of the polymorphisms of the TPMT gene in childhood ALL patients in Gaza Strip. Other types of mutation in TPMT gene may be responsible for the observed mylotoxicity among the investigated patients. Factors other than TPMT polymorphisms may also be responsible for the development of toxicity. Therefore, more studies are recommended to be performed in order to investigate such factors.
|Publisher||the islamic university|
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