ANALYSIS OF ALTERATIONS OF ONCOGENES AND TUMOR-SUPPRESSOR GENES IN CHRONIC LYMPHOCYTIC-LEUKEMIA

B cell chronic lymphocytic leukemia (B-CLL) represents the most freque nt adult leukemia in the Western world. The molecular pathogenesis of B-CLL is largely unknown. Although initial reports on small panels of cases had suggested a role for Bcl-1 and Bcl-2 oncogene activation in B-CLL, later investigations failed to confirm these data. Among tumor suppressor genes, p53 mutations have been reported in a fraction of ca ses. In this study, we have attempted a conclusive definition of the i nvolvement of dominantly acting oncogenes (Bcl-1 and Bcl-2) and tumor suppressor loci (p53, 6q(-)) in 100 cases of B-CLL selected for their CD5 positivity and Rai's stage (0 to IV). Rearrangements of Bcl-1 and Bcl-2 and deletions of 6q and 17p were analyzed by Southern blot using multiple probes. Mutational analysis (single strand conformation poly morphism and polymerase chain reaction direct sequencing) was used to assay p53 inactivation. No alterations of Bcl-1 or Bcl-2 were detected in the 100 cases tested. Mutations of p53 were found in 10/100 cases without any significant association with clinical stage. Deletions of 6q were present in 4/100 cases. Overall, our data indicate that: 1) co ntrary to previous reports, Bcl-1 and Bcl-2 rearrangements are not inv olved in CD5(+) and B-CLL pathogenesis and 2) p53 mutations are presen t in 10% of cases at all stages of the disease.