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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2899-2907
Detection of Clonal Hodgkin and Reed-Sternberg Cells With
Identical Somatically Mutated and Rearranged VH Genes
in Different Biopsies in Relapsed Hodgkin's Disease
Martina Vockerodt,
Marta Soares,
Holger Kanzler,
Ralf Küppers,
Dieter Kube,
Martin-Leo Hansmann,
Volker Diehl, and
Hans Tesch
From the Department of Internal Medicine I and the Institute for
Genetics, University of Cologne, Cologne, Germany; and the Department
of Pathology, University of Frankfurt, Frankfurt, Germany.
Hodgkin's disease (HD) represents a malignant lymphoma in which the
putative malignant Hodgkin and Reed-Sternberg (H-RS) cells are rare and
surrounded by abundant reactive cells. Single-cell analyses showed that
H-RS cells regularly bear clonal Ig gene rearrangements. However, there
is little information on the clinical evolution of HD in a given
patient. In this study, we used the single-cell polymerase chain
reaction (PCR) to identify H-RS cells with clonal Ig gene
rearrangements in biopsy specimens of patients with relapsed HD. The
obtained clonal variable region heavy-chain (VH) gene
rearrangements were used to construct tumor-clone-specific oligonucleotides spanning the complementarity determining region (CDR)
III and somatically mutated areas in the rearranged VH
gene. A number of biopsies were obtained during a period of 3 years from two HD patients. H-RS cells with identical VH
rearrangements were detected in two separate infiltrated lymph nodes
from one patient with nodular sclerosis HD. In a second patient with
mixed cellularity HD subtype, clonal VH rearrangements with
identical sequences were detected in infiltrated spleen and two lymph
node biopsies. Despite the high sensitivity of the PCR method used (one
clonal cell in 105 mononuclear cells), residual
H-RS cells were not found in peripheral blood, leukapheresis material,
purified CD34+ stem cells or bone marrow. The results
show that different specimens from relapsed patients suffering from
classical HD carry the same clonotypic IgH rearrangements with
identical somatic mutations, demonstrating the persistence and the
dissemination of a clonal tumor cell population. Thus, PCR assays with
CDRIII-specific probes derived from clonal H-RS cells are of clinical
importance in monitoring the dissemination of HD and tumor progression
and could be useful for analysis of minimal residual disease after
autologous stem cell transplantation.
© 1998 by The American Society of Hematology.
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