Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma NATURE COMMUNICATIONS Green, M. R., Vicente-Duenas, C., Romero-Camarero, I., Liu, C. L., Dai, B., Gonzalez-Herrero, I., Garcia-Ramirez, I., Alonso-Escudero, E., Iqbal, J., Chan, W. C., Campos-Sanchez, E., Orfao, A., Pintado, B., Flores, T., Blanco, O., Jimenez, R., Angel Martinez-Climent, J., Garcia Criado, F. J., Garcia Cenador, M. B., Zhao, S., Natkunam, Y., Lossos, I. S., Majeti, R., Melnick, A., Cobaleda, C., Alizadeh, A. A., Sanchez-Garcia, I. 2014; 5


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.

View details for DOI 10.1038/ncomms4904

View details for Web of Science ID 000338831000001