Loss of bHLH transcription factor E2A activity in primary effusion lymphoma confers resistance to apoptosis.
Similar to classical Hodgkin lymphoma (HL) tumour cells, primary effusion lymphoma (PEL) originates from mature B cells but displays a non-B cell phenotype, the mechanisms and consequences of which are not yet understood. This study showed that PEL lacked DNA binding activity of the B cell-determining transcription factors E2A, EBF and Pax5. PEL overexpressed the E2A antagonists ABF-1 and Id2, which have been described to block the B-cell differentiation program in classical HL. However, in contrast to HL cells, B lineage-inappropriate genes were not similarly upregulated in PEL, and reconstitution of B cell-specific E2A homodimer activity in PEL induced apoptosis. These data demonstrate that lineage infidelity in PEL is not as pronounced as in HL, and that the loss of the B cell-specific transcription factor E2A in PEL is implicated in apoptosis protection.
Lietz
Andreas
A
Max-Delbrück-Centre for Molecular Medicine, Berlin and Haematology, Oncology and Tumorimmunology, Chartié, Medical University Berlin, Berlin, Germany.
Janz
Martin
M
Sigvardsson
Mikael
M
Jundt
Franziska
F
Dörken
Bernd
B
Mathas
Stephan
S
D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; D015534:Trans-Activators; C081976:EBF1 protein, human; C497281:PAX5 protein, human; C407909:TCF3 protein, human