Nature Immunology 7 (2): 207-215 (2006-02)

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.; Doerken B.

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

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

Type: Article

PubMed: 16369535
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