Alterations of the retinoblastoma a susceptibility gene in chronic lymphocytic leukemia

Research in recent years has shown that malignant transformation is a genetic multistep process. This holds true not only for in-vitro model systems, but has also been elegantly shown in-vivo, as in colorectal cancer. Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries and occurs mainly in elderly patients, suggesting that in this form of leukemia, cumulative molecular lesions may be necessary for transformation. However, the molecular background is unknown in most cases. Cytogenetic aberrations may be used as markers for genes involved in the process of malignant transformation. In CLL, the most frequently observed structural cytogenetic lesion is a deletion/translocation involving the long arm of chromosome 13, a region where the retinoblastoma susceptibility gene (Rb-gene) has been mapped (13q14). Many groups have studied the question as to whether alterations of the Rb-gene play a causal role in the pathogenesis of CLL. This review deals with recent data indicating that i) the Rb-gene may be altered in a minority of CLL cases, and ii) there may be another gene localized on chromosome 13q14 that may be important in the molecular biology of CLL.