Asset Details
Do you wish to reserve the book?
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome
Do you wish to request the book?
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome
2017
Overview
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), including primary patient cells, have an increased sensitivity to
in vitro
sudemycin treatment relative to controls.
In vivo
sudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouring
U2AF1
mutations with pre-mRNA splicing modulators like sudemycins.
Spliceosome mutations occur in approximately 50% of patients with myelodysplastic syndromes. Here, the authors show that tumour cells harbouring the
S34F
mutation in the
U2AF
spliceosome gene is sensitive to compounds that further perturb the spliceosome.
