ORIGIN OF THE HODGKIN REED-STERNBERG CELLS IN CHRONIC LYMPHOCYTIC-LEUKEMIA WITH HODGKINS TRANSFORMATION/

A lymphoma with the characteristic features of Hodgkin's disease (HD) occasionally develops in patients with B-cell chronic lymphocytic leuk emia (CLL), and has been called Richter's syndrome with HD features, I n such cases, large tumor cells have the morphological and immunopheno typic features of classical Hodgkin and Reed-Sternberg (H-RS) cells. H owever, it is not known whether the H-RS cells arise from transformati on of the underlying CLL cells or from a different pathological proces s. We report herein a study of the clonal relationship between the CLL cells and the H-RS cells in three cases of Richter's syndrome with HD features by using a single cell assay. We isolated single CLL cells a nd H-RS cells from immunostained tissue sections by micromanipulation. The immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of each cell was amplified by the polymerase chain r eaction (PCR). The products were then compared by gel electrophoresis and nucleotide sequencing, The IgH CDRIII sequences from the H-RS cell s were identical to those from the CLL cells in two cases. In one case , the clonal relationship between the two types of cells could not be determined because PCR products could not be obtained from any of the H-RS cells. This study shows that the H-RS cells and the CLL cells bel ong to the same clonal population in some cases of Richter's syndrome with HD features. Furthermore, our findings indicate that mature B cel ls can undergo transformation to cells with the features of H-RS cells , in association with a cellular background typical of HD. This study also supports recent findings suggesting that the H-RS cells in classi cal HD are derived from transformed B cells. (C) 1998 by The American Society of Hematology.