DETECTION OF FOS, JUN AND RAS IN NEWLY-DIAGNOSED CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA BY IMMUNOCYTOCHEMISTRY AND PCR

The expression of the oncogenes c-fos, c-jun and c-pan-ras was analyze d at the protein level in newly diagnosed cases of acute lymphoblastic leukemia (ALL) in children. Blast cells obtained from 104 children wi th 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 h ad a significantly higher relapse frequency (p=0.0002). A similar tren d was found for Jun-positive ALL (p=0.073). In contrast, the expressio n of Ras showed no significant correlation with the relapse rate (p=0. 98). Corresponding results were obtained for the relapse-free interval s. The relapse-free intervals were higher in patients with Fos- and Ju n-positive leukemic cells than in patients with negative tumor cells ( Fos: p<0.001; Jun: p=0.09; Ras: p=NS, log-rank test). In order to subs tantiate the significant correlation of c-fos-protein expression with the relapse rate the c-fos-mRNA expression was investigated in a colle ctive of 20 patients by semi-quantitative PCR. The PCR-assay and immun ocytochemistry corresponded in 14 of 20 cases (70%). The results of th e PCR-assay demonstrated also a trend for increased c-fos-mRNA express ion and higher relapse rate.