title: Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia.
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.
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Belyea
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Pentz
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Medrano
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Minghong
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Bioinformatics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Turner
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Legallo
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Jones
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Tario
authors.affiliation: Department of Biological Sciences, Brock University, St Catharines, Ontario, L2S 3A1, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Gross
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Maria Luisa S
authors.initials: ML
authors.lastname: Sequeira-Lopez
authors.affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: R Ariel
authors.initials: RA
authors.lastname: Gomez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D015448:Leukemia, B-Cell / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007942:Leukemia, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D012083:Renin / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D055815:Young Adult
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; D012083:Renin