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 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<0.001; Jun: p=0.09; Ras: p=NS, log-rank test). In order to substantiate the significant correlation of c-fos-protein expression with the relapse rate the c-fos-mRNA expression was investigated in a collective of 20 patients by semi-quantitative PCR. The PCR-assay and immunocytochemistry corresponded in 14 of 20 cases (70%). The results of the PCR-assay demonstrated also a trend for increased c-fos-mRNA expression and higher relapse rate.