Mutations of retinoblastoma gene (Rb-1) as a prognostic factor in childrenwith acute leukemia and neuroblastoma

Rb-1 is a tumor suppressor gene encoding for a nuclear phosphoprotein actin g as a cell cycle regulator, normally expressed in hematopoietic cells and more often inactivated by point mutations with predominance for exons 20-24 . The aim of this study is to correlate the retinoblastoma-1 (Rb-1) gene mu tations with the prognosis and progression of childhood acute leukemia and neuroblastoma. Bone marrow slides from 26 children with leukemia (18 acute lymphoblastic leukemia [ALL] and 8 acute myeloid leukemia [AML]) and 4 chil dren with neuroblastoma were studied. Exons 20, 21, and 22 were amplified u sing the polymerase chain reaction technique. Single strand conformational polymorphism (SSCP) and heterodoublex analysis were performed to detect mut ations. In ALL cases, two samples in exon 20 (11.11%), one in exon 21 (5.56 %), and four in exon 22 (22.22%) had altered conformation. All but one of t hese cases were classified as high-risk leukemia patients who either relaps ed or never achieved remission. Two of the AML cases who did not achieve re mission and one of the neuroblastoma cases with concomitant bone marrow inf iltration had altered conformation as well. The SSCP and heterodoublex anal ysis showed that all but one who did not belong to the high-risk group had the same altered conformation. These data suggest that Rb-1 gene could poss ibly be used as an independent prognostic factor for the acute leukemia of childhood and result in the intensification of chemotherapy. In solid tumor s with bone marrow involvement it could play a role as a marker of aggressi ve disease.