Abstract
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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.