Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma

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Item Type:	Article
Title:	Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma
Creators Name:	Jundt, F., Acikgoez, O., Kwon, S.H., Schwarzer, R., Anagnostopoulos, I., Wiesner, B., Mathas, S., Hummel, M., Stein, H., Reichardt, H.M. and Doerken, B.
Abstract:	Plasticity of committed mouse B cells has been demonstrated by inactivation of the B-cell commitment transcription factor PAX5, resulting in loss of the B-cell phenotype and differentiation into various hematopoietic lineages. Furthermore, mature mouse B cells could be reprogrammed into macrophages by overexpression of myeloid-specific transcription factors. Here, we report that aberrant activity of the transmembrane receptor, Notch1, interferes with the B-lymphoid phenotype of mature human germinal center-derived B cells in Hodgkin lymphoma, so called Hodgkin and Reed-Sternberg cells. They have lost the B-cell phenotype despite their mature B-cell origin. Notch1 remodels the B-cell transcription factor network by antagonizing the key transcription factors E2A and early B-cell factor (EBF). Through this mechanism, B lineage-specific genes were suppressed and B lineage-inappropriate genes were induced. We provide evidence that absence of the Notch inhibitor Deltex1 contributes to deregulated Notch activity in Hodgkin and Reed-Sternberg cells. These data suggest that Notch activation interferes with dedifferentiation of neoplastic B cells in Hodgkin lymphoma.
Keywords:	Notch1, Hodgkin Lymphoma, Dedifferentiation, Transcription Factors, Animals, Mice
Source:	Leukemia
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Volume:	22
Number:	8
Page Range:	1587-1594
Date:	August 2008
Official Publication:	https://doi.org/10.1038/leu.2008.101
PubMed:	View item in PubMed

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