Molecular analysis of the retinoblastoma (RB1) gene in acute myeloid leukemia patients.

The pathogenesis of acute leukemia is still poorly understood. In the past few years several groups have reported deletion of the RB1 gene or altered pRB expression in certain hematologic malignancies, suggesting a possible role of RB1 gene inactivation in the process of leukemogenesis. Most studies regarding structural abnormalities of the RB1 gene indicate that gross deletions or rearrangements are present in a small percentage of patients with acute myeloid leukemia (AML), as is the case with retinoblastoma, where the majority of RB1 gene abnormalities are attributed to point mutations. To investigate if such point mutations in the RB1 gene may have a role in leukemogenesis in AML, we screened the RB1 gene of 36 AML patients using conformation-sensitive gel electrophoresis (CSGE). No point mutations were found in the 27 exons, their flanking intron regions or in the promoter region in any of the 36 patients. Thus, according to our findings, the susceptibility in these patients for developing AML does not appear to be related to point mutations in the RB1 gene. While screening for point mutations, we identified a number of new and previously noted neutral sequence variations indicating the efficiency and sensitivity of CSGE in identifying small changes in the RB1 gene.