GENETIC RELATEDNESS OF LYMPHOID MALIGNANCIES - TRANSFORMATION OF CHRONIC LYMPHOCYTIC-LEUKEMIA AS A MODEL

Objective: Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that devel op in about 10% of affected persons were reviewed. These B-cell cancer s include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. T wo possible relations were evaluated: development from the chronic lym phocytic leukemia clone (clonal evolution) and development of a geneti cally unrelated, independent second cancer. Data Sources: An English-l anguage medical literature search was done using MEDLINE (1982 to 1992 ) and CANCERLIT (1982 to 1992). An extensive manual search of the lite rature that included meeting abstracts and reports was also done. Appr oximately 500 articles, abstracts, and book chapters were identified; 102 were selected for detailed analysis. Data Analysis: Analysis of ge netic relatedness between the two cancers considered concordance for i mmunoglobulin gene rearrangements, for immunoglobulin isotypes and idi otypes, and for cytogenetic abnormalities. Conclusions: In the case of large B-cell lymphoma, generally thought to arise from the chronic ly mphocytic leukemia clone, approximately one half of the patients had g enetically unrelated cancers. In prolymphocytic transformation, all ca ses studied appeared to evolve from the chronic lymphocytic leukemia c lone. The few studies of acute lymphoblastic leukemia and multiple mye loma showed genetic relatedness in some cases and unrelatedness in oth ers. These data indicate that progression to more aggressive B-cell ca ncers in persons with chronic lymphocytic leukemia can result from eit her clonal evolution or from an independent transforming event.