CSNK1A1 mutations and gene expression analysis in myelodysplastic syndromes with del(5q)

Erica Bello; Andrea Pellagatti; Jacqueline Shaw; Cristina Mecucci; Rajko Kušec; Sally Killick; Aristoteles Giagounidis; Sophie Raynaud; María J Calasanz; Pierre Fenaux; Jacqueline Boultwood

doi:10.1111/bjh.13563

CSNK1A1 mutations and gene expression analysis in myelodysplastic syndromes with del(5q)

Br J Haematol. 2015 Oct;171(2):210-214. doi: 10.1111/bjh.13563. Epub 2015 Jun 18.

Authors

Erica Bello^{1

2}, Andrea Pellagatti^{1

2}, Jacqueline Shaw^{1

2}, Cristina Mecucci³, Rajko Kušec⁴, Sally Killick⁵, Aristoteles Giagounidis⁶, Sophie Raynaud⁷, María J Calasanz⁸, Pierre Fenaux⁹, Jacqueline Boultwood^{1

2}

Affiliations

¹ LLR Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
² NIHR Biomedical Research Centre, Oxford, UK.
³ Haematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy.
⁴ Dubrava University Hospital and Zagreb School of Medicine, University of Zagreb, Zagreb, Croatia.
⁵ Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK.
⁶ Department of Haematology, Oncology, and Palliative Care, Marienhospital Düsseldorf, Düsseldorf, Germany.
⁷ Centre Hospitalier Universitaire Nice, Nice, France.
⁸ Department of Genetics, University of Navarra, Pamplona, Spain.
⁹ Service d'hématologie seniors, Hôpital St Louis, Paris, France.

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).

Keywords: 5q- syndrome; CSNK1A1; del(5q); haploinsufficiency; mutation.