From eyedrops to potential leukaemia treatment

University of Nottingham | December 2018 | From eye drops to potential leukaemia treatment

Scientists at the University of Nottingham have found eye drops  have the potential to be used in treatment for an aggressive form of  blood cancer: acute myeloid leukaemia (AML).  Nottingham staff collaborated on research led by experts at the Wellcome Sanger Institute, University of Cambridge, and other scientists which led to the discovery that a compound identified in eye drops, being developed  to treat a form of eye disease, has shown promise for treating AML.The active ingredient in eye drops has the potential to treat AML, as it targets leukaemic blood cells without harming non-leukemic  blood cells. 

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Full details of the research are available from:

University of Nottingham [press release]

Wellcome Sanger Institute [press release]

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 MYBBRD4 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.

The full article is available to read from Nature Communications

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