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 m orphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (MD) can be found in a background of other wise typical B-CLL, To test these MRS-like cells for a potential clonal rel ationship to the B-CLL cells, single cells were micro-manipulated from immu nostained tissue sections, and rearranged immunoglobulin genes were amplifi ed 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 t hese cells from 2 distinct members of a germinal-center B-cell clone. Separ ate clonal V gene rearrangements were amplified from MRS-like and B-CLL cel ls from 2 other patients, showing concomitant presence of 2 distinct expand ed B-cell clones. Epstein Barr virus (EBV) was detected in the MRS-like cel ls 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 cas es, somatic mutations have been detected in the rearranged V genes of the M RS-like cells, and in 1 of the EBV-positive MRS-like cell clones, somatic m utations rendered an originally functional V gene rearrangement nonfunction al, We speculate that the MRS-like cells in B-CLL represent potential precu rsors for MRS cells causing HD. C) 2000 by The American Society of Hematology.