Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1023-1031
Hodgkin and Reed-Sternberg-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
Holger Kanzler,
Ralf Küppers,
Sabine Helmes,
Hans-Heinrich Wacker,
Andreas Chott,
Martin-Leo Hansmann, and
Klaus Rajewsky
From the Institute for Genetics and the Departments of Internal
Medicine and Pathology, University of Cologne, Cologne, Germany; the
Department of Hematopathology, University of Kiel, Kiel, Germany; the
Department of Clinical Pathology, Allgemeines Krankenhaus, Vienna,
Austria, and the Institute for Pathology, University of Frankfurt,
Frankfurt, Germany.
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 (HD) can be
found in a background of otherwise typical B-CLL. To test these
HRS-like cells for a potential clonal relationship to the B-CLL cells,
single cells were micromanipulated from immunostained tissue sections,
and rearranged immunoglobulin genes were amplified from
HRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct
somatic mutations were found in HRS-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 HRS-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 HRS-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 HRS-like cells in B-CLL, like HRS cells in HD, derive
from germinal-center B cells. In all cases, somatic mutations have been
detected in the rearranged V genes of the HRS-like cells, and
in 1 of the EBV-positive HRS-like cell clones, somatic mutations
rendered an originally functional V gene rearrangement
nonfunctional. We speculate that the HRS-like cells in B-CLL represent
potential precursors for HRS cells causing HD.
