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Abstract
SRPK1, a kinase involved in splicing regulation, is a potential therapeutic target for AML patients. Here, the authors show that SRPK1 inhibition changes isoform levels of key epigenetic regulators, including BRD4, and it has anti-tumor effects specifically against MLL-rearranged AML cells.
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1 Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK; Gurdon Institute and Department of Pathology, Cambridge, UK
2 Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK
3 Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK; Karaiskakio Foundation, Nicosia, Cyprus
4 Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, UK
5 Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Munich, Germany
6 Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK; Wellcome Trust–MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
7 UK Dementia Research Institute, University of Cambridge, Cambridge, UK
8 School of Chemistry, University of New South Wales, Sydney, Australia; Exonate Ltd, Milton Science Park, Cambridge, UK
9 School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, UK
10 School of Chemistry, University of New South Wales, Sydney, Australia
11 Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK; Wellcome Trust Sanger Institute, Genome Campus, Cambridge, UK
12 Cancer Molecular Diagnosis Laboratory, National Institute for Health Research, Biomedical Research Centre, University of Cambridge, Cambridge, UK
13 Wellcome Trust–MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; Department of Haematology, Cambridge University Hospitals NHS Trust, Cambridge, UK
14 H3 Biomedicine Inc., Cambridge, MA, USA
15 Gurdon Institute and Department of Pathology, Cambridge, UK
16 Institute of Molecular Oncology and Functional Genomics, Department of Medicine II and TranslaTUM Cancer Center, Technical University of Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, & German Cancer Consortium (DKTK), Heidelberg, Germany
17 Epigenetics DPU, Immunoinflammation and Oncology TA Unit, GSK Medicines Research Centre, Stevenage, UK
18 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; European Bioinformatics Institute, Wellcome Genome Campus, Cambridgeshire, UK; Stem Cell Genetics, Wellcome Trust Sanger Institute, Cambridge, UK
19 Exonate Ltd, Milton Science Park, Cambridge, UK
20 Department of Haematology, University of Cambridge, Cambridge, UK
21 Wellcome Trust Sanger Institute, Genome Campus, Cambridge, UK
22 Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, & German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatrics, Dr. von Hauner Children’s Hospital, Ludwig Maximilians University München, Munich, Germany
23 Exonate Ltd, Milton Science Park, Cambridge, UK; Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Queen′s Medical Centre, Nottingham, UK
24 Stem Cell Genetics, Wellcome Trust Sanger Institute, Cambridge, UK
25 Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK; Wellcome Trust–MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK