The clonal origin of two cell populations in Richter's syndrome

A case of Richter's syndrome was studied by morphology, immunohistochemistry, flow cytometry, and immunoglobulin gene rearrangement. Flow cytometric study clearly demonstrated two monoclonal populations. The use of double staining with CD 5/CD 19 antibodies accompanied by two-color flow cytometric analysis clearly defined the chronic lymphocytic leukemia population and separated it from the lymphoma population. Immunoglobulin heavy-chain gene analysis of blood and lymph node specimens revealed nonidentical as well as identical nongermline bands in these two populations. However, light-chain gene analysis demonstrated that both populations shared a common clonal origin. This result underscores the unreliability of using heavy chain genotype alone to identify clonal origin. Since post-rearrangement deletion, point mutation, and heavy chain switching occur in heavy chain genes, but are seldom seen in light chain genes, it is important to analyze both heavy and light chain genes to conclusively determine clonal origin.