title: CSNK1A1 mutations and gene expression analysis in myelodysplastic syndromes with del(5q).
abstract: Mutations of CSNK1A1, a gene mapping to the commonly deleted region of the 5q- syndrome, have been recently described in patients with del(5q) myelodysplastic syndromes (MDS). Haploinsufficiency of Csnk1a1 in mice has been shown to result in β-catenin activation and expansion of haematopoietic stem cells (HSC). We have screened a large cohort of 104 del(5q) MDS patients and have identified mutations of CSNK1A1 in five cases (approximately 5%). We have shown up-regulation of β-catenin target genes in the HSC of patients with del(5q) MDS. Our data further support a central role of CSNK1A1 in the pathogenesis of MDS with del(5q).
authors.affiliation: LLR Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|NIHR Biomedical Research Centre, Oxford, UK.
authors.forename: Erica
authors.initials: E
authors.lastname: Bello
authors.affiliation: LLR Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|NIHR Biomedical Research Centre, Oxford, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pellagatti
authors.affiliation: LLR Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|NIHR Biomedical Research Centre, Oxford, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Shaw
authors.affiliation: Haematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.affiliation: Dubrava University Hospital and Zagreb School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Rajko
authors.initials: R
authors.lastname: Kušec
authors.affiliation: Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Killick
authors.affiliation: Department of Haematology, Oncology, and Palliative Care, Marienhospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.affiliation: Centre Hospitalier Universitaire Nice, Nice, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Raynaud
authors.affiliation: Department of Genetics, University of Navarra, Pamplona, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
authors.affiliation: Service d'hématologie seniors, Hôpital St Louis, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.affiliation: LLR Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|NIHR Biomedical Research Centre, Oxford, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
keywords: 5q- syndrome; CSNK1A1; del(5q); haploinsufficiency; mutation