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

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. and Acikgoez, O. and Kwon, S.H. and Schwarzer, R. and Anagnostopoulos, I. and Wiesner, B. and Mathas, S. and Hummel, M. and Stein, H. and 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 (U.K.)
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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