Genetic relatedness of lymphoid malignancies. Transformation of chronic lymphocytic leukemia as a model

Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer.

An English-language medical literature search was done using MEDLINE (1982 to 1992) and CANCERLIT (1982 to 1992). An extensive manual search of the literature that included meeting abstracts and reports was also done. Approximately 500 articles, abstracts, and book chapters were identified; 102 were selected for detailed analysis.

Analysis of genetic relatedness between the two cancers considered concordance for immunoglobulin gene rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic abnormalities.

In the case of large B-cell lymphoma, generally thought to arise from the chronic lymphocytic leukemia clone, approximately one half of the patients had genetically unrelated cancers. In prolymphocytic transformation, all cases studied appeared to evolve from the chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic leukemia and multiple myeloma showed genetic relatedness in some cases and unrelatedness in others. These data indicate that progression to more aggressive B-cell cancers in persons with chronic lymphocytic leukemia can result from either clonal evolution or from an independent transforming event.