Clinical Profile and Outcome of Adult Classical Hodgkin’s Lymphoma: Real World Single Centre Experience

Jacob, Linu Abraham; Begum, Tarjina; Halder, Arkoprovo; Babu, M. C. Suresh; Lokesh, K. N.; Rudresha, A. H.; Rajeev, L. K.; Saldanha, Smitha C.

doi:10.1007/s12288-024-01735-9

Indian J Hematol Blood Transfus

2024

DOI: 10.1007/s12288-024-01735-9

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Clinical Profile and Outcome of Adult Classical Hodgkin’s Lymphoma: Real World Single Centre Experience

Linu Abraham Jacob,

Tarjina Begum,

Arkoprovo Halder

et al.

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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

Knecht,

Petrogiannis-Haliotis,

Louis

et al. 2024

Cells

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The bi- or multinucleated Reed–Sternberg cell (RS) is the diagnostic cornerstone of Epstein–Barr 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.

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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

Knecht,

Petrogiannis-Haliotis,

Louis

et al. 2024

Cells

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show abstract

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Clinical Profile and Outcome of Adult Classical Hodgkin’s Lymphoma: Real World Single Centre Experience

Cited by 1 publication

References 28 publications

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

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

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