Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia Journal Article


Authors: Minuesa, G.; Albanese, S. K.; Xie, W.; Kazansky, Y.; Worroll, D.; Chow, A.; Schurer, A.; Park, S. M.; Rotsides, C. Z.; Taggart, J.; Rizzi, A.; Naden, L. N.; Chou, T.; Gourkanti, S.; Cappel, D.; Passarelli, M. C.; Fairchild, L.; Adura, C.; Glickman, J. F.; Schulman, J.; Famulare, C.; Patel, M.; Eibl, J. K.; Ross, G. M.; Bhattacharya, S.; Tan, D. S.; Leslie, C. S.; Beuming, T.; Patel, D. J.; Goldgur, Y.; Chodera, J. D.; Kharas, M. G.
Article Title: Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia
Abstract: The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08–2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI’s oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer. © 2019, The Author(s).
Keywords: murinae
Journal Title: Nature Communications
Volume: 10
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2019-06-19
Start Page: 2691
Language: English
DOI: 10.1038/s41467-019-10523-3
PROVIDER: scopus
PMCID: PMC6584500
PUBMED: 31217428
DOI/URL:
Notes: Source: Scopus
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