Expression and prognostic value of the retinoblastoma tumour suppressor gene (RB‐1) in childhood acute lymphoblastic leukaemia

Abstract

In a retrospective analysis, acute lymphoblastic leukaemia (ALL) blast cells of 102 children were investigated for the expression of the retinoblastoma susceptibility (RB)-1 gene at mRNA level by dot blot hybridization and semiquantitative RT-PCR. 56 patients were analysed by dot blot hybridization and 35 representative patients out of this group by semiquantitative RT-PCR. Two additional groups of patients (23 patients with initial and 23 patients with relapsed ALL) were also investigated by semiquantitative RT-PCR. RB-1 gene expression was detectable in all investigated ALL at different levels. According to the relative mRNA expression the patients were discriminated by the median value in groups with low or high RB-1 expression. The Kaplan-Meier estimates showed that patients with low RB-1 expression had a lower probability of remaining in first remission (P=0.03) and a significantly higher risk to succumb to their disease (P=0.03). Furthermore, the comparison of the results between initial and relapsed ALL showed that the relapses had significantly lower RB-1 mRNA expression (P=0.02). The overall survival of the patients was shorter in both groups when RB-1 gene expression was low. A multivariate analysis, including age, sex, immunological subtype, initial white blood cell count and RB-1 expression, identified RB-1 as an independent prognostic predictor (P=0.017) in addition to the initial white blood cell count (P=0.00001). In conclusion, low RB-1 expression is an unfavourable prognostic predictor in initial and relapsed childhood ALL. The RB-1 gene expression in relapsed ALL is significantly lower than in initial ALL.