Abstract
Our understanding of the tumorigenesis of classical Hodgkin lymphoma (cHL) and the formation of Reed–Sternberg cells (RS-cells) has evolved drastically in the last decades. More recently, a better characterization of the signaling pathways and the cellular interactions at play have paved the way for new targeted therapy in the hopes of improving outcomes. However, important gaps in knowledge remain that may hold the key for significant changes of paradigm in this lymphoma. Here, we discuss the past, present, and future of cHL, and review in detail the more recent discoveries pertaining to genetic instability, anti-apoptotic signaling pathways, the tumoral microenvironment, and host-immune system evasion in cHL.
Highlights
Our understanding of classical Hodgkin lymphoma has evolved from that of a mysterious disease characterized by grossly disfigured cells to that of a lymphoma with a complex biology that may hold the key to its cure
In 2017, using 3D TRF2/Telo-Q-FISH we proved that TRF2 directly bound to telomeres was shown to be lost progressively during the transition from H- to RS-cells in LMP1-expressing tumor cells of classical Hodgkin lymphoma (cHL), leading to the formation of ghost cells [64,70]
The above-mentioned findings in both EBV negative and EBV positive cHL have convincingly demonstrated that the evolution of H-cells into RS-cells is orchestrated by a disruption in the shelterin protein complex which leads to telomere vulnerability, loss of size, disorganized fusions, and multi-centric chromosomes
Summary
Our understanding of classical Hodgkin lymphoma (cHL) has evolved from that of a mysterious disease characterized by grossly disfigured cells to that of a lymphoma with a complex biology that may hold the key to its cure. Unifying to the pathognomonic multinucleated Reed–Sternberg cells (RS-cells) in all subtypes is the loss of the B-cell markers CD19 and CD20 and expression of CD15 and CD30, their paucity among the total amount of cells within the affected tissue, and the presence of EBV positive and negative forms [1,2]. This aggressive disease, affecting children, adolescents, adults, and elderly, of poor prognosis when advanced at diagnosis or relapsing/refractory, has caught the imagination of researchers for nearly two centuries. We present the landmark discoveries that paved the way to the modern understanding of cHL biology and aim to tell the story of the Hodgkin (H) and Reed–Sternberg (RS) cells using some of the most recent evidence in the field
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