Matches in SemOpenAlex for { <https://semopenalex.org/work/W2904132382> ?p ?o ?g. }
- W2904132382 abstract "Abstract We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonged survival of mice transplanted with MLL -rearranged AML. RNA-seq analysis demonstrates that SRPK1 inhibition leads to altered isoform levels of many genes including several with established roles in leukemogenesis such as MYB , BRD4 and MED24 . We focus on BRD4 as its main isoforms have distinct molecular properties and find that SRPK1 inhibition produces a significant switch from the short to the long isoform at the mRNA and protein levels. This was associated with BRD4 eviction from genomic loci involved in leukemogenesis including BCL2 and MYC . We go on to show that this switch mediates at least part of the anti-leukemic effects of SRPK1 inhibition. Our findings reveal that SRPK1 represents a plausible new therapeutic target against AML." @default.
- W2904132382 created "2018-12-22" @default.
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- W2904132382 date "2018-12-19" @default.
- W2904132382 modified "2023-10-01" @default.
- W2904132382 title "SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4" @default.
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- W2904132382 doi "https://doi.org/10.1038/s41467-018-07620-0" @default.
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