Determination of thiopurine s-methyltransferase gene mutation in the patients with acute lymphoblastic leukemia

This study was carried out in order to investigate the Thiopurine S-Methyltransferase gene mutation in the patients with childhood an adult acute lymphoblastic leukemia using 6-Mercaptopurin for treatment. Patients who were diagnosed as ALL and received treatment in Dicle University Faculty of Medicine Departments of Pediatric and Adult Hematology between July 2007 and 2010 were enrolled to this study. Totally 55 patients were included, 22 of them were adults and 33 were children.Three different TPMT gene mutation (TPMT*2,TPMT*3B and TPMT*3C) were tested in all patients in the molecular hematology laboratory with the Real Time PCR method. TPMT*2 gene mutation (heterozygosity and homozygote) was detected as negative in all patients. In 2 of the patients TPMT*3B gene mutation was detected as heterozygote (3,6%). It was detected as dual heterozygosity (TPMT*3B and TPMT*3C) in 2 of the patients (3,6%). No homozygote mutant individual was detected.In 5 of the adult patients, leukopenia developed during the treatment period. In 4 of these patients, no TPMT polymorphism was detected but 6-Mercaptopurin dose was decreased due to the leukopenia (the rate of 25%). In other adult patient, TPMT*3B heterozygosity was detected and 6-Mercaptopurin dose was decreased at the rate of 50% due to the leukopenia. It was observed that because of the leukopenia and the infections the treatment was paused once. Leukopenia was detected in 30 of the children patients who continued the treatment. Also it was observed that the treatment of 2 of them, being TPMT*3B and TPMT*3C dual heterozygote, was quitted from time to time due to leukopenia and infection. It was observed that because of the leukopenia and the infections the treatment was paused in one child patient who was detected TPMT*3B heterozygote too. In remaining 27 children patients no TMPT polymorphisms were detected and leukopenia led to a decrease in the dose (between 25%- 50%). After the decreases in the dose and pauses in the treatment, recovery was observed in the leukopenia. In five children patients that TMPT polymorphisms were not detected, hepatotoxicity symptoms were observed.In the patients with TMPT polymorphisms, Standard dose of mercaptopurin in the treatment can cause severe toxicity (the main adverse effect is leukopenia). For this reason, in the patients developing clear leukopenia after the use of 6-mercaptopurin, analyzing the TMPT mutation is highly important. Thus, individual dose adjustment maximises the efficiency of treatment and minimises the adverse effects, possible mortality and the costs of treatment. This study which is one of the the first studies related to TPMT mutations in our region forms a basis for the future extensive population studies.