Reprogramming of B lymphoid cells in human lymphoma pathogenesis.

Abstract

Previous hypotheses have stated that differentiated cells lose the ability to change their fate. Using lymphoid development as a model system, recent data have challenged this rigid view of cellular differentiation. It has been shown in mouse models that, under certain conditions, even mature lymphoid cells can display a broad developmental potential, and might even transdifferentiate into other cell types. The relevance of these observations for the physiological ontogenesis of lymphoid cells or their malignant transformation is currently unclear. Recent data from our laboratory have demonstrated that similar processes can be observed in the malignant Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL), a common B cell-derived lymphoma. In HRS cells, the B cell-specific homodimer activity of the transcription factor E2A is functionally disrupted by overexpression of the E2A antagonists activated B cell factor 1 (ABF-1) and inhibitor of differentiation 2 (Id2). In consequence, the expression of B cell-specific genes is lost, and B lineage-inappropriate genes are upregulated. These data have demonstrated the plasticity of human lymphoid cells and offer an explanation for the unique phenotype of cHL. We first summarize data showing the plasticity of lymphoid cells in mouse models, second describe our observations regarding the altered B cell-specific transcription factor network in HRS cells, and third discuss the possible implications of these findings for human lymphoma pathogenesis.

• Authors: Martin Janz, Bernd Dörken, Stephan Mathas
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 5 Issue 10 Pg. 1057-61 (May 2006) ISSN: 1551-4005 [Electronic] United States
• PMID: 16687930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Inhibitor of Differentiation Protein 2
• MSC protein, human
• TCF3 protein, human

Topics

• Animals
• B-Lymphocytes (metabolism, pathology)
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Cell Differentiation
• Cell Line, Tumor
• Cell Lineage
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Hodgkin Disease
• Humans
• Inhibitor of Differentiation Protein 2 (genetics, metabolism)
• Reed-Sternberg Cells (metabolism, pathology)