APPROACH TO THIOPURINE
METHYTRANSFERANSE VARIATION AS A QUANTITATIVE PARAMETER FOR INDIVIDUAL
CHEMOTHERAPY OF MERCATOPURINE
Gu L-J, Ye Q-D, Liang A-B, Zhao J-C, Xue H-L, Tang Y-N, Chen J
Shanghai Children’s Medical Center, Shanghai, China
Objective: To approach to the activity and genotype of Thiopurine
methyltransferase (TPMT) and the concentration of thioguanine nucleotides
as a quantitative parameter for individualization of using mercapurine
(6MP).
Methods: The erythrocyte TPMT activity were measured by means of radiochemical
assay. PCR-SSP and PCR-RFLP were used to determine the mutations in genomic
DNAs. Erythrocyte TGNs concentration was studied by high-performance liquid
chromatograph.
Results: The TPMT activity in the total 371 Han population was 16.64±4.50U/ml pRBCs (Man 16.78±4.96 U/ml pRBCs, Woman 16.52±4.44 U/ml pRBCs). 8.1 percents of the sample
have the activity lower than 10 U/ml pRBCs. There are no differences of
TPMT activity in gender, age, and between healthy and patient with ALL.
There were 5 cases as TPMT*2 genotype，4 TPMT*3A，6 TPMT*3B，and 10 TPMT*3C in the subjects who had
low TPMT activity. The genotypes of the other 5 subjects were still
unknown. In children with ALL, the TGNs concentration did show a negative
relationship to TPMT activity measured at diagnosis and WBC count measured
on the 14th day after the determination of TGNs.
Conclusion: TPMT activity, it’s genotypes, and TGNs may become objective
quantitative parameters for the individualization of 6MP chemotherapy in children
with ALL.