Thiopurine methyltransferase genotyping in Palestinian childhood acute lymphoblastic leukemia patients.

BACKGROUND

The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT2 (238G>C), TPMT3B (c.460G>A), TPMT3A (c.460G>A and c.719A>G) and TPMT3C (c.719A>G). The aim of the present study was to determine the frequency of 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 Gaza strip hospitals were analyzed. Genomic DNA from peripheral blood leukocytes was isolated and the TPMT2, TPMT3B TPMT3A and TPMT3C allelic polymorphism was determined by PCR-RFLP and allele specific PCR technique.

RESULTS

No TPMT*2, 3B or 3C alleles were detected. Only one, out of 56 patients, was found heterozygous for the TPMT3A allele. Thus, the frequency of TPMT3A allele was calculated to be 0.89%. Fourteen patients of ALL were suffering from myelotoxicity during 6-MP 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.

CONCLUSION

TPMT*3A was the only deficiency allele detected in our population with an allelic frequency of 0.89%. Other polymorphic alleles in TPMT gene, or factors other than TPMT polymorphisms may be responsible for the development of myelosuppression in cases that don't carry the investigated TPMT alleles (*2, *3A, *3B and *3C). Therefore, more studies are recommended to study such factors.