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

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Listed:
  • Michael R. Green

    (School of Medicine, Stanford University)

  • Carolina Vicente-Dueñas

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Isabel Romero-Camarero

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Chih Long Liu

    (School of Medicine, Stanford University)

  • Bo Dai

    (School of Medicine, Stanford University)

  • Inés González-Herrero

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Idoia García-Ramírez

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Esther Alonso-Escudero

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Javeed Iqbal

    (University of Nebraska Medical Center)

  • Wing C. Chan

    (University of Nebraska Medical Center)

  • Elena Campos-Sanchez

    (Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma de Madrid, c/Nicolás Cabrera, n° 1, Campus de Cantoblanco)

  • Alberto Orfao

    (Universidad de Salamanca)

  • Belén Pintado

    (Genetically Engineered Mouse Facility, CNB-CSIC)

  • Teresa Flores

    (Institute of Biomedical Research of Salamanca (IBSAL)
    Universidad de Salamanca)

  • Oscar Blanco

    (Universidad de Salamanca)

  • Rafael Jiménez

    (Institute of Biomedical Research of Salamanca (IBSAL)
    Universidad de Salamanca, Campus M. Unamuno s/n)

  • Jose Angel Martínez-Climent

    (Center for Applied Medical Research (CIMA), University of Navarra)

  • Francisco Javier García Criado

    (Universidad de Salamanca)

  • María Begoña García Cenador

    (Universidad de Salamanca)

  • Shuchun Zhao

    (Stanford University School of Medicine)

  • Yasodha Natkunam

    (Stanford University School of Medicine)

  • Izidore S. Lossos

    (University of Miami, Sylvester Comprehensive Cancer Center)

  • Ravindra Majeti

    (School of Medicine, Stanford University)

  • Ari Melnick

    (Weill Cornell Medical College)

  • César Cobaleda

    (Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma de Madrid, c/Nicolás Cabrera, n° 1, Campus de Cantoblanco)

  • Ash A. Alizadeh

    (School of Medicine, Stanford University)

  • Isidro Sánchez-García

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n
    Institute of Biomedical Research of Salamanca (IBSAL))

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.

Suggested Citation

  • 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 & Ele, 2014. "Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4904
    DOI: 10.1038/ncomms4904
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