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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.

Authors :
Mathas S
Janz M
Hummel F
Hummel M
Wollert-Wulf B
Lusatis S
Anagnostopoulos I
Lietz A
Sigvardsson M
Jundt F
Jöhrens K
Bommert K
Stein H
Dörken B
Source :
Nature immunology [Nat Immunol] 2006 Feb; Vol. 7 (2), pp. 207-15. Date of Electronic Publication: 2005 Dec 20.
Publication Year :
2006

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.

Details

Language :
English
ISSN :
1529-2908
Volume :
7
Issue :
2
Database :
MEDLINE
Journal :
Nature immunology
Publication Type :
Academic Journal
Accession number :
16369535
Full Text :
https://doi.org/10.1038/ni1285