3D structural and functional characterization of the transition from Hodgkin to Reed-Sternberg cells.
Recent research using an innovative 3D quantitative FISH approach of nuclear remodelling associated with the transition from mononuclear Hodgkin to diagnostic multinuclear Reed-Sternberg cells revealed profound changes in the 3D nuclear organization of telomeres. Analogous 3D telomere dynamics were identified in Hodgkin's lymphoma derived cell-lines and diagnostic patient biopsies. These changes were observed in both, EBV positive and EBV-negative Hodgkin's lymphoma and independent of the age of the patients at presentation. Compared to mononuclear Hodgkin cells, multinuclear Reed-Sternberg cells are characterized by a highly significant increase of telomere aggregates, often composed of very short telomeres, telomere shortening and loss. RS-cells with telomere free "ghost" nuclei are regularly observed. The telomere protecting shelterin complex appears to be disrupted and deregulation of DNA-repair mechanisms is observed. Our findings are consistent with the hypothesis that distinct 3D telomere changes and shelterin disruption represent a common pathogenetic denominator in the generation of Reed-Sternberg cells.
Knecht
Hans
H
Division d'Hématologie, CHUS, Université de Sherbrooke, Sherbrooke, Québec, Canada. hans.knecht@usherbrooke.ca
Brüderlein
Silke
S
Mai
Sabine
S
Möller
Peter
P
Sawan
Bassem
B
D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D016539:Reed-Sternberg Cells / Q000473:pathology / Q000648:ultrastructure*; D016615:Telomere / Q000648:ultrastructure*