Therapeutic targeting of myeloid leukemias with spliceosomal mutations through modulation of splicing catalysis

ABSTRACT: Mutations in spliceosomal genes are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations occur at highly restricted amino acid residues and perturb normal splice site and exon recognition. Spliceosomal mutations are always heterozygous and rarely co-occur with one another, suggesting that cells may only tolerate a partial deviation from normal splicing activity. To test this hypothesis, we generated mice with inducible hemizygous expression of the commonly occurring SRSF2P95H mutation in the hematopoietic system. These mice rapidly developed lethal bone marrow failure upon activation of the Srsf2P95H mutation with concomitant deletion of the wildtype Srsf2 allele, demonstrating that Srsf2-mutant cells depend on the wildtype Srsf2

ORGANISM(S): Mus musculus

SUBMITTER: Heidi Dvinge 

PROVIDER: E-GEOD-74064 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress