Dihydrofolate-reductase and thymidylate-synthase in childhood acute lymphoblastic leukemia

The expression of thymidylate-synthase (TS) and dihydrofolate-reductase (DHFR) was analysed immunohistochemically in 110 initial and 28 relapsed childhood acute lymphoblastic leukemia (ALL). Relapse-rates were not significantly higher in initial ALL with overexpression of TS- and DHFR than in ALL without overexpression of the proteins. In addition, the disease-free survival was not different for patients with TS or DHFR-negative and TS- or DHFR-positive ALL. No differences were found in the overall survival times of patients with relapsed ALL and with or without expression of TS or DHFR. Of the initial ALL 42% showed TS-overexpression, whereas of the relapsed ALL 64% of the cases were TS-positive (p = 0.03). The corresponding values for DHFR were 20% and 32% (p = 0.18). The results demonstrate clearly that expression of the proteins TS and DHFR has no importance for the resistance of ALL although the proteins increase during treatment.