title: Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma.
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.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany. smathas@mdc-berlin.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Mathas
authors.forename: Martin
authors.initials: M
authors.lastname: Janz
authors.forename: Franziska
authors.initials: F
authors.lastname: Hummel
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wollert-Wulf
authors.forename: Simone
authors.initials: S
authors.lastname: Lusatis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: Andreas
authors.initials: A
authors.lastname: Lietz
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens
authors.forename: Kurt
authors.initials: K
authors.lastname: Bommert
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019281:Dimerization; D015870:Gene Expression; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051797:Inhibitor of Differentiation Protein 2; D046912:Multiprotein Complexes; D051757:PAX5 Transcription Factor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C497450:ID2 protein, human; C112467:MSC protein, human; C497281:PAX5 protein, human; C407909:TCF3 protein, human