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

Gerard Minuesa, Steven K. Albanese, Wei Xie, Yaniv Kazansky, Daniel Worroll, Arthur Chow, Alexandra Schurer, Sun Mi Park, Christina Z. Rotsides, James Taggart, Andrea Rizzi, Levi N. Naden, Timothy Chou, Saroj Gourkanti, Daniel Cappel, Maria C. Passarelli, Lauren Fairchild, Carolina Adura, J. Fraser Glickman, Jessica SchulmanChristopher Famulare, Minal Patel, Joseph K. Eibl, Gregory M. Ross, Shibani Bhattacharya, Derek S. Tan, Christina S. Leslie, Thijs Beuming, Dinshaw J. Patel, Yehuda Goldgur, John D. Chodera, Michael G. Kharas

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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.

Original languageEnglish
Article number2691
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2019
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Physics and Astronomy (all)


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