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Thirty-four children with newly diagnosed acute nonlymphoblastic leukemia were analysed for the expression of P-glycoprotein (P-170), glutathione S-transferase-pi, (GST-pi) topoisomerase II (Topo II) and the proliferation antigen Ki-67 by the streptavidin-biotin-peroxidase method. Overexpression of P-170 was present in 26 cases (76%) and GST-pi overexpression was seen in 11 patients (32%). Down regulation of Topo II was found in 16 patients (47%) and Ki-67 positive cells (>5%) were detectable in 9 patients (26%). The remission rate was not influenced by P-170 or GST-pi expression, whereas patients with down regulation of Topo II or low Ki-67 expression had lower remission rates. The data were not significant. The probability of continuous first remission (CR) was lower in patients with P-170 expression (p=0.09). A significantly lower probability of CR was also seen in patients with low proliferative activity (p=0.03, log-rank test). The expression of the resistance proteins and the proliferative activity were found to be independent of the clinical parameters age, sex, FAB-type, and initial white blood cell count.

One hundred and eleven children with initial ALL and 28 children with relapsed ALL were analyzed immunohistochemically for expression of resistance-related proteins. P-glycoprotein (P-170) was found in 35% (initial ALL) vs 54% (relapsed ALL; p=0.07), glutathione S-transferase-pi (GST) in 49% vs 68% (p=0.07), thymidylate-synthase (TS) in 42% vs 64% (p=0.03), dihydrofolate-reductase (DHFR) in 20% vs 32% and metallothionein (MT) in 33% vs 32% of the cases. In initial ALL, the resistance proteins P-170 and GST were expressed more frequently in patients who relapsed under therapy and the frequency was similar to relapsed ALL. These results indicate that P-170 and GST-pi were already present before treatment. In contrast, expression of TS increased during treatment.

The expression of the oncogenes c-fos, c-jun and c-pan-ras was analyzed at the protein level in newly diagnosed cases of acute lymphoblastic leukemia (ALL) in children. Blast cells obtained from 104 children with untreated ALL were determined by the streptavidin-biotin-peroxidase method and specific antibodies. Of the ALL 52 cases were positive for Fos (50%), 65 for Jun (63%), and 22 for Ras (21%). Fos-positive ALL had a significantly higher relapse frequency (p=0.0002). A similar trend was found for Jun-positive ALL (p=0.073). In contrast, the expression of Ras showed no significant correlation with the relapse rate (p=0.98). Corresponding results were obtained for the relapse-free intervals. The relapse-free intervals were higher in patients with Fos- and Jun-positive leukemic cells than in patients with negative tumor cells (Fos: p

The expression of protein kinase C (PKC) was analysed in newly diagnosed cases of non-B acute lymphoblastic leukemia (NB-ALL) in children. Blast cells obtained from 104 children with untreated NB-ALL were analysed using the streptavidin-biotin-peroxidase method and the antibody MC5. Of the 104 patients with NB-ALL, 48 (=46%) showed positive staining for PKC. The relapse rate was significantly higher in NB-ALL with expression of PKC than in leukemia without expression of PKC (p=0.008). The relapse-free intervals in the PKC-negative leukemias were significantly longer than in cases of PKC-positive leukemias (p=0.004). The overall survival times were also longer in NB-ALL without expression of PKC than in ALL with PKC-expression (p=0.03). The results of univariate and multivariate analyses demonstrate that in addition to the clinical prognostic indicators PKC expression is a significant prognostic factor for relapse rate, relapse-free intervals, and overall survival times in NB-ALL of children.