MULTIPLE RESISTANCE MECHANISMS IN ACUTE NONLYMPHOBLASTIC LEUKEMIA (ANLL)

The expression of the resistance-related proteins P-glycoprotein 170 ( P-170) glutathione-S-transferase pi (GST-pi) topoisomerase II (Topo II ), thymidylate synthase (TS) and metallothionein (MT) was investigated in leukemic cells of 19 children with newly diagnosed acute nonlympho blastic leukemia. P-170 was expressed in 84 % GST-pi in 37 % TS in 47 % MT in 68 % and Topo II was downregulated in 37 % of the cases invest igated. No resistance factors were found in two patients, one positive factor was found in two patients three factors in three patients, fou r factors in 7 patients, and all resistance factors investigated were present in one patient. Patients who developed a relapse expressed mor e than two resistance mechanisms significantly more often than patient s who remained in remission (p=0,005). The probability of continuous f irst remission was significantly lower where more than two resistance mechanisms were expressed. The results indicate that the higher the nu mber of resistance-related proteins in childhood ANLL the poorer the p rognosis of the patients.