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Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma

Item Type:Article
Title:Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma
Creators Name:Mathas, S., Janz, M., Hummel, F., Hummel, M., Wollert-Wulf, B., Lusatis, S., Anagnostopoulos, I., Lietz, A., Sigvardsson, M., Jundt, F., Joehrens, K., Bommert, K., Stein, H. and Doerken, B.
Abstract:B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell-determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.
Keywords:B-Cell-Specific Activator Protein, B-Lymphocytes, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Tumor Cell Line, Dimerization, Gene Expression, Hodgkin Disease, Inhibitor of Differentiation Protein 2, Multiprotein Complexes, Phenotype, Messenger RNA, Neoplasm RNA
Source:Nature Immunology
ISSN:1529-2908
Publisher:Nature Publishing Group
Volume:7
Number:2
Page Range:207-215
Date:February 2006
Official Publication:https://doi.org/10.1038/ni1285
PubMed:View item in PubMed

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