The Hodgkin and Reed/Sternberg cell

Area of Science:

• Hematology
• Oncology
• Cell Biology

Background:

• Hodgkin and Reed/Sternberg (HRS) cells are the defining neoplastic cells in Hodgkin's lymphoma (HL).
• These cells exhibit unique morphological and immunophenotypic characteristics, distinguishing them from normal cellular counterparts.
• Despite their scarcity, HRS cells are the clonal drivers of HL pathogenesis.

Purpose of the Study:

• To elucidate the cellular origin and key pathogenetic mechanisms of Hodgkin and Reed/Sternberg cells.
• To understand the role of signaling pathways in HRS cell survival and HL development.

Main Methods:

• Analysis of HRS cell morphology and immunophenotype.
• Investigation of somatic mutations in immunoglobulin V genes.
• Examination of aberrant signaling pathway activation, including NF-kappaB.

Main Results:

• HRS cells predominantly originate from B cells, specifically suggesting a derivation from pre-apoptotic germinal center B cells based on mutation patterns.
• Aberrant activation of signaling pathways, notably the NF-kappaB pathway, is crucial for HRS cell survival.
• HRS or similar cells can be found in other conditions like non-Hodgkin lymphomas and infectious mononucleosis.

Conclusions:

• Hodgkin's lymphoma pathogenesis involves HRS cells derived mainly from germinal center B cells.
• Aberrant signaling pathways are critical for the survival of these malignant B cells.
• The study provides insights into the cellular origins and survival mechanisms of HRS cells in HL.