Article
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome.
Nature communications - 9 Jan 2017
Shirai Cara Lunn, White Brian S, Tripathi Manorama, Tapia Roberto, Ley James N, Ndonwi Matthew, Kim Sanghyun, Shao Jin, Carver Alexa, Saez Borja, Fulton Robert S, Fronick Catrina, O'Laughlin Michelle, Lagisetti Chandraiah, Webb Thomas R, Graubert Timothy A, Walter Matthew J
Abstract excerpt
Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F),...
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