Significance of TPMT activity and TGNs level detection for individualizing 6-mercaptopurine chemotherapy / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the activity and genotype of thiopurine methyltransferase (TPMT) and the concentration of thioguanine nucleotides (TGNs) as parameters for individualizing mercaptopurine (6-MP) therapy.</p><p><b>METHODS</b>Erythrocyte TPMT activity was measured by means of radiochemical assay. Sequence specific primer (SSP) PCR and restriction fragment length polymorphism (RFLP) were used to determine the mutations in TPMT genomic DNAs. Erythrocyte TGNs concentration in acute lymphoblastic leukemia (ALL) patients after 6-MP treatment was detected by high-performance liquid chromatography (HPLC).</p><p><b>RESULTS</b>The erythrocyte TPMT activity in Han population was 16.6 +/- 4.5U/ml pRBCs (man 16.8 +/- 5.0 U/ml pRBCs, woman 16.5 +/- 4.4 U/ml pRBCs), the activity in 8.1% of the samples was lower than 10 U/ml pRBCs. There was no difference for TPMT activity by gender, age, and between healthy donors and ALL patients. For TPMT genotypes, there were 5 cases of TPMT * 2, 4 TPMT * 3A, 6 TPMT * 3B, 10 TPMT * 3C and 5 unknown in 30 subjects who had low TPMT activity. In children with ALL, the TGNs level did show a negative correlation with TPMT activity at diagnosis and 7 approximately 14 days after 6-MP therapy and with WBC count 14 days after the determination of TGNs.</p><p><b>CONCLUSION</b>Detection of TPMT activity before 6-MP therapy and TGNs level during 6-MP therapy may be helpful for preventing side effects from antipurine metabolic drug overdose, and individualizing 6-MP chemotherapy in children with ALL.</p>