Hodgkin's lymphoma-derived tissue serially transplanted into severe
combined immunodeficient mice
U Kapp, J Wolf, M Hummel, M Pawlita, C von Kalle, F Dallenbach, M Schwonzen, GR Krueger, N Muller-Lantzsch and C Fonatsch
Medizinische Klinik I fur Innere Medizin, Universitat zu Koln, Germany.
Hodgkin (H) and Reed-Sternberg (RS) cells are considered to be the
malignant cell population in Hodgkin's disease (HD). To date, their
analysis has been hampered by their scarcity in primary tumors, poor growth
in vitro, and lack of an animal model. To establish an in vivo system for
the characterization of the malignant cells in HD, tumor biopsy samples
from 13 HD patients were transplanted beneath the renal capsule or into the
liver of severe combined immunodeficient (SCID) mice. HD-derived tissue
from three patients gave rise to human tumors in SCID mice. Three different
histologic patterns were observed: (1) lymphoproliferative disease (LPD),
(2) anaplastic large cell lymphoma (ALCL), (3) Hodgkin-like lesions (HDLL).
Immunohistochemical analysis showed that the tumors consisted of activated
B cells (CD30+, CD20+). Epstein-Barr virus (EBV)-encoded transcripts were
found in 80% to 100% of the tumor cells, although H and RS cells in the
primary tumors of two patients were EBV-. All tumors examined (3 of 3) and
the majority (6 of 10) of cell lines recultured in vitro had an abnormal
karyotype. Southern blot analysis of the human Ig heavy chain gene showed
that monoclonal or oligoclonal tumors of different B-cell origin grew in
the SCID mice from the same germ line-configurated primary biopsy specimen.
Our data suggest that the human cells in the SCID mice have either been
derived from EBV superinfected H and RS cells or from EBV-infected
bystander cells. If the latter is true, then these bystander cells must be
genetically abnormal. The genetic defect would be either aneuploidy or
instable euploidy. In either case, the cells might proliferate into
malignant aneuploid HDLL or ALCL under the influence of EBV and the special
environment encountered in the SCID mice.
Volume 82,
Issue 4,
pp. 1247-1256,
08/15/1993
Copyright © 1993 by The American Society of Hematology
