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Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia

Author

Listed:
  • Brian C. Belyea

    (University of Virginia School of Medicine)

  • Fang Xu

    (University of Virginia School of Medicine)

  • Ellen S. Pentz

    (University of Virginia School of Medicine)

  • Silvia Medrano

    (University of Virginia School of Medicine)

  • Minghong Li

    (University of Virginia School of Medicine)

  • Yan Hu

    (University of Virginia School of Medicine)

  • Stephen Turner

    (University of Virginia School of Medicine)

  • Robin Legallo

    (University of Virginia School of Medicine)

  • Craig A. Jones

    (Roswell Park Cancer Institute)

  • Joseph D. Tario

    (Roswell Park Cancer Institute)

  • Ping Liang

    (Brock University)

  • Kenneth W. Gross

    (Roswell Park Cancer Institute)

  • Maria Luisa S. Sequeira-Lopez

    (University of Virginia School of Medicine)

  • R. Ariel Gomez

    (University of Virginia School of Medicine)

Abstract

The cell of origin and triggering events for leukaemia are mostly unknown. Here we show that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene programme and constrains lymphocyte differentiation, facilitated by H3K4me3 activating marks in genes that control the pre-B stage. Mutant cells undergo neoplastic transformation, and mice develop a highly penetrant B-cell leukaemia with multi-organ infiltration and early death. These renin-expressing cells appear uniquely vulnerable as other conditional models of RBP-J deletion do not result in leukaemia. The discovery of these unique renin progenitors in the bone marrow and the model of leukaemia described herein may enhance our understanding of normal and neoplastic haematopoiesis.

Suggested Citation

  • Brian C. Belyea & Fang Xu & Ellen S. Pentz & Silvia Medrano & Minghong Li & Yan Hu & Stephen Turner & Robin Legallo & Craig A. Jones & Joseph D. Tario & Ping Liang & Kenneth W. Gross & Maria Luisa S. , 2014. "Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4273
    DOI: 10.1038/ncomms4273
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