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.
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.
Kanzler
H
H
Institute for Genetics, Department of Internal Medicine, University of Cologne, Cologne, Germany.
Küppers
R
R
Helmes
S
S
Wacker
H H
HH
Chott
A
A
Hansmann
M L
ML
Rajewsky
K
K
D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D054278:Embryonal Carcinoma Stem Cells; D020031:Epstein-Barr Virus Infections / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008875:Middle Aged; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000473:pathology*; D016133:Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000473:pathology*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014412:Tumor Virus Infections / Q000473:pathology
D004273:DNA, Neoplasm; D007135:Immunoglobulin Variable Region