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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MSK Authors
  1. Derek S Tan
    92 Tan
  2. Dinshaw J Patel
    479 Patel
  3. Yehuda Goldgur
    42 Goldgur
  4. Christina Leslie
    191 Leslie
  5. Minal A Patel
    71 Patel
  6. Michael Kharas
    100 Kharas
  7. Sun Mi Park
    23 Park
  8. John Damon Chodera
    120 Chodera
  9. James Christopher Taggart
    14 Taggart
  10. Arthur W Chow
    17 Chow
  11. Timothy Chou
    13 Chou
  12. Andrea Rizzi
    10 Rizzi
  13. Wei Xie
    19 Xie
  14. Alexandra Schurer
    15 Schurer
  15. Levi Naden
    2 Naden