Journal article
BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms
BS Wyspiańska, AJ Bannister, I Barbieri, J Nangalia, A Godfrey, FJ Calero-Nieto, S Robson, I Rioja, J Li, M Wiese, E Cannizzaro, MA Dawson, B Huntly, RK Prinjha, AR Green, B Gottgens, T Kouzarides
Leukemia | NATURE PUBLISHING GROUP | Published : 2014
DOI: 10.1038/leu.2013.234
Abstract
Small molecule inhibition of the BET family of proteins, which bind acetylated lysines within histones, has been shown to have a marked therapeutic benefit in pre-clinical models of mixed lineage leukemia (MLL) fusion protein-driven leukemias. Here, we report that I-BET151, a highly specific BET family bromodomain inhibitor, leads to growth inhibition in a human erythroleukemic (HEL) cell line as well as in erythroid precursors isolated from polycythemia vera patients. One of the genes most highly downregulated by I-BET151 was LMO2, an important oncogenic regulator of hematopoietic stem cell development and erythropoiesis. We previously reported that LMO2 transcription is dependent upon Janu..
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Awarded by Leukemia and Lymphoma Research
Funding Acknowledgements
We thank members of the Kouzarides laboratory for the thoughtful discussion. The Kouzarides laboratory was supported by Cancer Research UK, Leukaemia and Lymphoma Research, GlaxoSmithKline and BBSRC. Work in the Green laboratory is supported by Leukemia and Lymphoma Research, Cancer Research UK, the Kay Kendall Leukaemia Fund, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre, and the Leukemia and Lymphoma Society of America. The Gottgens laboratory was supported by Cancer Research UK and Leukaemia and Lymphoma Research, UK. The Huntly laboratory was supported by Cancer Research UK and Leukaemia and Lymphoma Research, UK. MA Dawson is a Wellcome Trust Beit Fellow and E Cannizzaro and M Wiese are funded by this Fellowship.