Tumor Suppressor Genes and Clonal Evolution in B-CLL

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Abstract
This review highlights the genetic alterations that have been detailed in the malignant B-cell clones of patients with B-chronic lymphocytic leukemia (CLL). In particular, the alterations seen in p53 and the retinoblastoma (Rb) genes are reviewed. In addition, the multiplicity of cytogenetic alterations observed at baseline and on sequential analysis are summarized. The cytogenetic and molecular biologic analysis of B-CLL clones has revealed that there is a dynamic array of genetic events which occur within a B-cell clone. This latter data strongly suggests that clonal evolution may occur in B-CLL patients. However the relationship of the clonal instability to the patient's clinical course is still unclear. The relatively frequent detection of multiple tumor suppressor gene alterations in the B-CLL clones offer several interesting clues regarding the transformation event within B-CLL. A model is proposed which attempts to explain the potential contribution and interaction of p53 and Rb gene alterations in a malignant B-cell transformation.