James N Ley

TL;DR: In this paper, the authors examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model.

TL;DR: It is found that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity to in vitro sudemycin treatment relative to controls, suggesting a potential for treating haem atological cancers harbouring U2 AF1 mutations with pre-mRNA splicing modulators like sudemies.

TL;DR: It is hypothesized that cells harboring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the splicingosome by splicing modulator drugs, providing a new treatment approach for patients with U2AF1 mutations.

TL;DR: The discovery of recurrent heterozygous missense mutations in U2AF1 in 11% of patients with myelodysplastic syndromes (MDS) suggests that perturbations in pre-mRNA splicing play a role in MDS pathogenesis.

TL;DR: To study the effects of U2AF1(S34F) expression on hematopoiesis, a site-specific, single-copy, doxycycline-inducible (controlled by the reverse tetracycline-transactivator [rtTA] transgene) U2 AF1(WT) and U2af1 (S 34F) transgenic mice were created and a doxy cycline dose-dependent increase in expression was observed.