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

AuthorsGreen, Michael R.; Vicente-Dueñas, Carolina ; Romero-Camarero, Isabel ; González-Herrero, Inés ; Alonso-Escudero, Esther ; Campos-Sánchez, Elena; Orfao, Alberto ; Pintado, Belén; Flores, Teresa; Blanco, Óscar; Jiménez, Rafael; Martínez-Climent, José Ángel; García-Criado, Francisco Javier; García-Cenador, Begoña; Lossos, Izidore S.; Cobaleda, César ; Alizadeh, Ash A.; Sánchez García, Isidro
Issue DateJun-2014
PublisherNature Publishing Group
CitationNature Communications 5: 3904 (2014)
AbstractDiffuse 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. © 2014 Macmillan Publishers Limited. All rights reserved.
DescriptionPMCID: PMC4321731.-- et al.
Publisher version (URL)http://dx.doi.org/10.1038/ncomms4904
Identifiersissn: 2041-1723
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