J. Delabie et al., PHENOTYPE, GENOTYPE AND CLONALITY OF REED-STERNBERG CELLS IN NODULAR SCLEROSIS HODGKINS-DISEASE - RESULTS OF A SINGLE-CELL STUDY, British Journal of Haematology, 94(1), 1996, pp. 198-205
The genotype and clonality of Reed-Sternberg (RS) cells in Hodgkin's d
isease (HD) has remained a controversial issue, largely due to the sca
rcity of RS cells in tissues and the limitations of the techniques use
d to resolve this issue, Southern hybridization and polymerase chain r
eaction (PCR) assays using DNA extracted from tissues can only documen
t clonal gene rearrangements, but do not indicate which cellular popul
ation is responsible for such rearrangements, To overcome the limitati
ons of these previous techniques for studying the genotype and clonali
ty of RS cells, we analysed single RS cells with a single-cell PCR ass
ay to detect immunoglobulin heavy chain gene (IgH) rearrangements and
X-chromosome inactivation, Six cases of nodular sclerosis (NS) HD were
studied, The RS cells displayed a B-cell phenotype in three cases and
a null-cell phenotype in the other three cases, IgH rearrangements we
re detected in the RS cells of the three cases with a B-cell phenotype
, but not in the other cases, In these three cases the IgH rearrangeme
nts in the RS cells were polyclonal, although a subpopulation of clona
l RS cells was documented in one case. The finding that the RS cells w
ith IgH rearrangements were not monoclonal was supported in one case b
y studying the pattern of X-chromosome inactivation in single RS cells
by a single-cell human androgen receptor gene (HUMARA) PCR assay. Our
results indicate that NSHD begins as a polyclonal process in which a
clonal RS cell population may arise: and that the RS cells in a subset
of NSHD show evidence of B-lineage differentiation.