Histologische, immunhistochemische und molekularbiologische Charakterisierung retrovirusinduzierter, muriner hämatopoietischer Neoplasien [thesis]

Sandra Kunder
Histological, immunhistochemical and molecular biological characterisation of retrovirus-induced murine haematopoietic neoplasms The murine leukaemia virus Akv has lymphomagenic properties in newborn inbred NMRI mice. The enhancer in the U3 long terminal repeat sequence of the Akv genome is a major determinant of retroviral lymphomagenesis. In this study, the pathogenicity of wild-type Akv, Akv1-99, an Akv lacking one 99 bp repeat in the U3 sequence, and a panel of ten Akv1-99 mutants
more » ... mutations in the different transcription factor binding sites, was analysed. The retrovirus-induced haematopoietic tumours were classified according to the Bethesda Proposals (94, 138), based on histological and immunohistochemical analyses, and IgH gene rearrangements. All viruses were pathogenic. Tumour incidence ranged from 90 % to 100 %. The mutant viruses, however, differed in their latency periods and tissue specificity. Akv induced diffuse large B-cell lymphomas (32.5 %), follicular B-cell lymphomas (22.5 %), splenic marginal zone lymphomas (5 %), small B-cell lymphomas (5 %), and plasmacytomas (35 %). The mutant viruses induced almost exclusively plasmacytomas (up to 100 %). The latency periods of three mutant viruses were comparable to that of Akv; six mutant viruses showed a shorter latency (five latency periods were significantly shorter), and two mutant viruses with an additional mutation in the EGRE binding site induced tumours after significantly prolonged latency. These results suggest that mutations of transcription factor binding sites in the Akv enhancer maintained the pathogenicity of the viruses but resulted in a smaller spectrum of haematopoietic tumours with different impact on the latency. Comprehensive histological, immunohistochemical, and molecular analyses of 323 retrovirus-induced haematopoietic tumours (83.8 % plasmacytomas, 6.9 % diffuse large B-cell lymphomas, 4.5 % follicular B-cell lymphomas, 4.2 % splenic marginal zone lymphomas, 1.2 % small B-cell lymphomas, 1.2 % acute myeloid leukaemia [...]
doi:10.5282/edoc.5424 fatcat:6j4pxifa4vgqpmwcazyziur5gq