Clarke, M., Volpe, G., Sheriff, L. et al. (6 more authors) (2017) Transcriptional regulation of SPROUTY 2 by MYB influences myeloid cell proliferation and stem cell properties by enhancing responsiveness to IL-3. Leukemia, 31. pp. 957-966. ISSN 0887-6924
Abstract
Myeloproliferative neoplasms (MPN), which overproduce blood cells in the bone marrow, have recently been linked with a genetically determined decrease in expression of the MYB transcription factor. Here, we use a mouse MYB knockdown model with an MPN-like phenotype to show how lower levels of MYB lead to stem cell characteristics in myeloid progenitors. The altered progenitor properties feature elevated cytokine responsiveness, especially to IL-3, which results from increased receptor expression and increased MAPK activity leading to enhanced phosphorylation of a key regulator of protein synthesis, ribosomal protein S6. MYB acts on MAPK signaling by directly regulating transcription of the gene encoding the negative modulator SPRY2. This mechanistic insight points to pathways that might be targeted therapeutically in MPN.Leukemia accepted article preview online, 17 October 2016. doi:10.1038/leu.2016.289.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The authors. This is an author produced version of a paper subsequently published in Leukemia. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Nov 2016 10:47 |
Last Modified: | 29 Jan 2018 10:15 |
Published Version: | https://doi.org/10.1038/leu.2016.289 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/leu.2016.289 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:106327 |