Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage, whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the nondeleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target.

Detaljer

Författare
  • Rebekka K. Schneider
  • Vera Ademà
  • Dirk Heckl
  • Marcus Järås
  • Mar Mallo
  • Allegra M. Lord
  • Lisa P. Chu
  • Marie E. McConkey
  • Rafael Kramann
  • Ann Mullally
  • Rafael Bejar
  • Francesc Solé
  • Benjamin L. Ebert
Externa organisationer
  • Brigham and Women's Hospital / Harvard Medical School
  • Autonomous University of Barcelona
  • Hospital del Mar Medical Research Institute
  • University of California, San Diego
  • Massachusetts Institute of Technology
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)509-520
Antal sidor12
TidskriftCancer Cell
Volym26
Utgivningsnummer4
StatusPublished - 2014 okt 13
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa