Molecular pathogenesis of Epstein-Barr virus associated posttransplant lymphomas: New insights through latent membrane protein 1 fingerprinting

Citation
H. Schafer et al., Molecular pathogenesis of Epstein-Barr virus associated posttransplant lymphomas: New insights through latent membrane protein 1 fingerprinting, TRANSPLANT, 72(3), 2001, pp. 492-496
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
TRANSPLANTATION
ISSN journal
0041-1337 → ACNP
Volume
72
Issue
3
Year of publication
2001
Pages
492 - 496
Database
ISI
SICI code
0041-1337(20010815)72:3<492:MPOEVA>2.0.ZU;2-4
Abstract
Background. Fingerprint amino acid patterns within the carboxy terminus of the latent membrane protein (LMP1) oncoprotein of Epstein-Barr virus (EBV) allow individual strain identification at the molecular level. LMP1 is expr essed in the tumor cells of EBV-associated posttransplant lymphomas (PTLs) and the LMP1 genome is also identified in lymphocytes of most donors of all ogeneic bone marrow. Therefore, LMP1 genotyping in donor lymphocytes and PT L tumor cells, together with sex chromatin determination of tumor cells, al lows to determine the origin of PTL tumor cells and the origin of individua l EBV strains harboured by them. Methods. We traced the origin of aggressive PTLs occurring in six patients after allogeneic T cell-depleted stem cell transplantation (allo-SCT). DNA was extracted from donor lymphocytes and PTLs of recipients and amplified w ith LMP1-specific primers in each case. A comparative sequence analysis of the fingerprint LMP1 region identified in donor lymphocytes and lymphoma wa s performed. Results. One lymphoma of donor origin occurred after highly selected CD34PBSCT and contained the same LMP1 genotype as the donor lymphocytes. Three lymphomas of recipient origin had deletions within the carboxy terminus of LMP1, not identified in the donor strains. All lymphomas occurred in the se tting of allo-SCT and had a rapid clinical course. Conclusions. These results show that highly selected CD34+ PBSCT does not p rotect against transfer of EBV positive founder cells of donor type PTL and that, after allo-SCT, recipient type PTLs are not uncommon. Outgrowth of r ecipient type lymphoma may be favoured by LMP1 deletion variant strains pre sent in recipient lymphocytes.