DHPLC Determination of TPMT Polymorphisms.

Acute Lymphoblastic Leukemia

thiopurines, thiopurine methyl transferase, toxicity, pharmacogenomics

TPMT is a key enzyme in the metabolism of thiopurines. TPMT polymorphisms have been described and are associated with a decrease activity of such enzyme. Therefore, a higher risk of developing toxicity is present in patients requiring these drugs, which are indicated in acute lymphoblastic leukemia, as well as, immunosuppressors after organ transplantation. The frequency of heterozygotes polymorphisms ranges from 3 till 12 %, in different populations. Homozygous patients have a lower frequency, estimated 1 in 300 individuals. The frequency of such polymorphisms in mestizos mexican population has not been analyzed, and we considered important to determine this frequency in healthy and patients requiring thiopurines, particularly acute lymphoblastic leukemia.

Objectives: Determine by DHPLC analysis the frequency of TPMT polymorphisms in mestizos mexican population with acute lymphoblastic leukemia. * To do a clinical correlation between the presence of polymorphism and thiopurine related- myelotoxicity. * Inclusion criteria: Healthy volunteers or patients with acute lymphoblastic leukemia, age \> 18 years, who attend to the National Institute of Cancerologia. * Exclussion criteria: Patients with ALL, who are unable to have an adequate follow-up. * Samples: Genomic DNA from peripheral blood leukocytes was isolated by standard methods. Known (wild-type and polymorphic) sequenced polymerase chain reaction (PCR) fragments of the TPMT gene were used as controls. TPMT gene fragments were amplified. PCR products were then analyzed by denaturating high performance liquid chromatography (DHPLC).

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