Hodgkin and Reed-Stemberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones:: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease

In rare cases of B-cell chronic lymphocytic leukemia (B-CLL), large cells morphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (MD) can be found in a background of otherwise typical B-CLL, To test these MRS-like cells for a potential clonal relationship to the B-CLL cells, single cells were micro-manipulated from immunostained tissue sections, and rearranged immunoglobulin genes were amplified from MRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct somatic mutations were found in MRS-like and B-CLL cells from 1 patient, which indicates derivation of these cells from 2 distinct members of a germinal-center B-cell clone. Separate clonal V gene rearrangements were amplified from MRS-like and B-CLL cells from 2 other patients, showing concomitant presence of 2 distinct expanded B-cell clones. Epstein Barr virus (EBV) was detected in the MRS-like cells of these 2 latter cases, indicating clonal expansion of an EBV-harboring B cell in the setting of B-CLL, There is evidence that MRS-like cells in B-CLL, like HRS cells in MD, derive from germinal-center B cells. In all cases, somatic mutations have been detected in the rearranged V genes of the MRS-like cells, and in 1 of the EBV-positive MRS-like cell clones, somatic mutations rendered an originally functional V gene rearrangement nonfunctional, We speculate that the MRS-like cells in B-CLL represent potential precursors for MRS cells causing HD. C) 2000 by The American Society of Hematology.