{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T21:34:35Z","timestamp":1780868075753,"version":"3.54.1"},"reference-count":131,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The bi- or multinucleated Reed\u2013Sternberg cell (RS) is the diagnostic cornerstone of Epstein\u2013Barr Virus (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 GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere\/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage\/bridge\/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC\/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy 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.<\/jats:p>","DOI":"10.3390\/cells13211748","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T04:28:43Z","timestamp":1729657723000},"page":"1748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["3D-Q-FISH\/Telomere\/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere\/Shelterin\/Lamin AC Complex as the Common Pathogenic, Molecular\/Spatial Denominator of Classical Hodgkin Lymphoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7909-7866","authenticated-orcid":false,"given":"Hans","family":"Knecht","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Petrogiannis-Haliotis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Jewish General Hospital, McGill University, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"Louis","sequence":"additional","affiliation":[{"name":"Telo Genomics Corp., Ontario, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-2201","authenticated-orcid":false,"given":"Sabine","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1177\/095952873201700106","article-title":"On some Morbid Appearances of the Absorbent Glands and Spleen","volume":"17","author":"Hodgkin","year":"1832","journal-title":"Med. 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