Background: The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most\r\npopulations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are\r\nTPMT*2 (238G>C), TPMT*3B (c.460G>A), TPMT*3A (c.460G>A and c.719A>G) and TPMT*3C (c.719A>G). The aim of\r\nthe present study was to determine the frequency of TPMT polymorphisms and their association with the\r\noccurrence of adverse events, during 6-mercaptopurine therapy in pediatric acute lymphoblastic leukemic (ALL)\r\npatients in Gaza Strip.\r\nMethods: A total of 56 DNA samples from all pediatric ALL patients admitted to the pediatric hematology\r\ndepartments of Gaza strip hospitals were analyzed. Genomic DNA from peripheral blood leukocytes was isolated\r\nand the TPMT*2, TPMT*3B TPMT*3A and TPMT*3C allelic polymorphism was determined by PCR-RFLP and allele\r\nspecific PCR technique.\r\nResults: No TPMT*2, *3B or *3C alleles were detected. Only one, out of 56 patients, was found heterozygous for the\r\nTPMT*3A allele. Thus, the frequency of TPMT*3A allele was calculated to be 0.89%. Fourteen patients of ALL were\r\nsuffering from myelotoxicity during 6-MP therapy. From our results, no significant association could be established\r\nbetween clinical and laboratory data and/or the presence of the mutation in TPMT gene.\r\nConclusion: TPMT*3A was the only deficiency allele detected in our population with an allelic frequency of 0.89%.\r\nOther polymorphic alleles in TPMT gene, or factors other than TPMT polymorphisms may be responsible for the\r\ndevelopment of myelosuppression in cases that don�t carry the investigated TPMT alleles (*2, *3A, *3B and *3C).\r\nTherefore, more studies are recommended to study such factors.
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