Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma

Michael R. Green, Carolina Vicente-Dueñas, Isabel Romero-Camarero, Chih Long Liu, Bo Dai, Inés González-Herrero, Idoia García-Ramírez, Esther Alonso-Escudero, Javeed Iqbal, Wing C. Chan, Elena Campos-Sanchez, Alberto Orfao, Belén Pintado, Teresa Flores, Oscar Blanco, Rafael Jiménez, Jose Angel Martínez-Climent, Francisco Javier García Criado, María Begoña García Cenador, Shuchun ZhaoYasodha Natkunam, Izidore S. Lossos, Ravindra Majeti, Ari Melnick, César Cobaleda, Ash A. Alizadeh, Isidro Sánchez-García

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal centre B-cells (GCB-like) or activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human haematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by hit-and-run oncogenesis. We model this hit-and-run mechanism by transiently expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6 may function in a hit-and-run role in lymphomagenesis.

Original languageEnglish (US)
Article number3904
JournalNature communications
Volume5
DOIs
StatePublished - Jun 2 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Green, M. R., Vicente-Dueñas, C., Romero-Camarero, I., Long Liu, C., Dai, B., González-Herrero, I., García-Ramírez, I., Alonso-Escudero, E., Iqbal, J., Chan, W. C., Campos-Sanchez, E., Orfao, A., Pintado, B., Flores, T., Blanco, O., Jiménez, R., Martínez-Climent, J. A., Criado, F. J. G., Cenador, M. B. G., ... Sánchez-García, I. (2014). Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma. Nature communications, 5, [3904]. https://doi.org/10.1038/ncomms4904