Role of Casein Kinase 1A1 in the Biology and Targeted Therapy of Del(5q) MDS

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2014 Sep 23

PMID 25242043

Citations 93

Authors

Rebekka K Schneider

Vera Adema

Dirk Heckl

Marcus Jaras

Mar Mallo

Allegra M Lord

Lisa P Chu

Marie E McConkey

Rafael Kramann

Ann Mullally

Rafael Bejar

Francesc Sole

Benjamin L Ebert

Affiliations

Soon will be listed here.

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.

Citing Articles

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