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Ig rearrangements in isolated Reed-Sternberg cells: conclusions from four different studies
M Hummel1, T Marafioti, K Ziemann
1Institute of Pathology, Klinikum Benjamin Franklin, Free University Berlin, Germany.
Insights
Investigating the cellular origin of Hodgkin
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- The cellular origin and proliferation of Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) remain debated.
- Immunohistochemical and molecular studies yield conflicting results regarding B-cell or T-cell features in HRS cells.
- Cytogenetic analyses for clonality have not provided conclusive evidence.
Purpose of the Study:
- To definitively determine the cellular origin and clonality of HRS cells.
- To resolve contradictory findings in previous immunohistochemical and molecular studies.
- To clarify the B-cell or T-cell lineage of HRS cells in Hodgkin's disease.
Main Methods:
- Isolation of single HRS cells from Hodgkin's disease patients.
- Amplification of immunoglobulin (Ig) gene rearrangements within isolated HRS cells.
- Analysis of Ig rearrangements to infer cellular lineage and clonality.
Main Results:
- Most studies found Ig rearrangements in HRS cells, suggesting a B-cell origin for these Hodgkin's disease cases.
- Individual IgH rearrangements were detected in some HD cases.
- A majority of cases exhibited monoclonal HRS cells, sometimes with additional polyclonal rearranged HRS cells.
Conclusions:
- Evidence from Ig rearrangements strongly indicates a B-cell origin for HRS cells in most Hodgkin's disease cases.
- The presence of monoclonal HRS cells supports their role as the malignant population in HD.
- Variations in findings across studies may be due to the selection of patient cases for investigation.
Abstract:
The cellular origin and the type of proliferation of the Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of Hodgkin's disease (HD), is an issue of constant debate. Immunohistochemical and molecularbiological studies of different research groups revealed contradictory results among the different groups ranging from a complete absence to a frequent presence of B-cell or T-cell characteristic features in the HRS cells. The determination of their clonality by cytogenetic means produced no conclusive results. To unequivocally clarify these questions we and others isolated single HRS cells and amplified their immunoglobulin (Ig) rearrangements. Most groups found Ig rearrangements within the HRS cells pointing to a B-cell nature of these HD cases. Individual IgH rearrangements were found in a proportion of the HD cases whereas most cases harbor monoclonal HRS cells with or without additional polyclonal rearranged HRS cells. Further studies are needed to clarify whether the differences among the different groups are caused by the selection of the HD cases used for investigation.