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Nat Commun. 2014;5:3273. doi: 10.1038/ncomms4273.

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

Author information

1
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
2
Department of Bioinformatics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
3
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
4
Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
5
Department of Biological Sciences, Brock University, St Catharines, Ontario, L2S 3A1, Canada.

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.

PMID:
24549417
PMCID:
PMC3929784
DOI:
10.1038/ncomms4273
[Indexed for MEDLINE]
Free PMC Article
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