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3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma
Version 1
: Received: 5 August 2024 / Approved: 5 August 2024 / Online: 6 August 2024 (12:35:18 CEST)
How to cite:
Knecht, H.; Petrogiannis-Haliotis, P.; Louis, S.; Mai, S. 3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma. Preprints2024, 2024080366. https://doi.org/10.20944/preprints202408.0366.v1
Knecht, H.; Petrogiannis-Haliotis, P.; Louis, S.; Mai, S. 3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma. Preprints 2024, 2024080366. https://doi.org/10.20944/preprints202408.0366.v1
Knecht, H.; Petrogiannis-Haliotis, P.; Louis, S.; Mai, S. 3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma. Preprints2024, 2024080366. https://doi.org/10.20944/preprints202408.0366.v1
APA Style
Knecht, H., Petrogiannis-Haliotis, P., Louis, S., & Mai, S. (2024). 3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma. Preprints. https://doi.org/10.20944/preprints202408.0366.v1
Chicago/Turabian Style
Knecht, H., Sherif Louis and Sabine Mai. 2024 "3D-Q-FISH/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/ Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma" Preprints. https://doi.org/10.20944/preprints202408.0366.v1
Abstract
The bi- or multi-nucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of EBV-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC) derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: i) to be of germinal center-derived B-cell origin, ii) to be EBV-negative to avoid EBV latency III expression, and iii) to support permanent LMP1 expression upon induction. These conditions are unified in the EBV-, Diffuse Large B-Cell Lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstuctive nanotechnology revealed spatial, quantititive and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, further progression during transition to RS-like cells, including progressive complexity of the karytotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed on diagnostic patient samples and correlate with clincal outcome. Moreover, in vitro signficant disturbance of the lamin AC/telomere interaction progressively occured. In summary, our research over the past three decades identifed cHL as the first lymphoid maligancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
