MSI2 is required for maintaining activated myelodysplastic syndrome stem cells

James Taggart, Tzu Chieh Ho, Elianna Amin, Haiming Xu, Trevor S. Barlowe, Alexendar R. Perez, Benjamin H. Durham, Patrick Tivnan, Rachel Okabe, Arthur Chow, Ly Vu, Sun Mi Park, Camila Prieto, Christopher Famulare, Minal Patel, Christopher J. Lengner, Amit Verma, Gail Roboz, Monica Guzman, Virginia M. KlimekOmar Abdel-Wahab, Christina Leslie, Stephen D. Nimer, Michael G. Kharas

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Myelodysplastic syndromes (MDS) are driven by complex genetic and epigenetic alterations. The MSI2 RNA-binding protein has been demonstrated to have a role in acute myeloid leukaemia and stem cell function, but its role in MDS is unknown. Here, we demonstrate that elevated MSI2 expression correlates with poor survival in MDS. Conditional deletion of Msi2 in a mouse model of MDS results in a rapid loss of MDS haematopoietic stem and progenitor cells (HSPCs) and reverses the clinical features of MDS. Inversely, inducible overexpression of MSI2 drives myeloid disease progression. The MDS HSPCs remain dependent on MSI2 expression after disease initiation. Furthermore, MSI2 expression expands and maintains a more activated (G1) MDS HSPC. Gene expression profiling of HSPCs from the MSI2 MDS mice identifies a signature that correlates with poor survival in MDS patients. Overall, we identify a role for MSI2 in MDS representing a therapeutic target in this disease.

Original languageEnglish (US)
Article number10739
JournalNature communications
StatePublished - Feb 22 2016

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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