MSI2 is required for maintaining activated myelodysplastic syndrome stem cells Journal Article

Authors: Taggart, J.; Ho, T. C.; Amin, E.; Xu, H.; Barlowe, T. S.; Perez, A. R.; Durham, B. H.; Tivnan, P.; Okabe, R.; Chow, A.; Vu, L.; Park, S. M.; Prieto, C.; Famulare, C.; Patel, M.; Lengner, C. J.; Verma, A.; Roboz, G.; Guzman, M.; Klimek, V. M.; Abdel-Wahab, O.; Leslie, C.; Nimer, S. D.; Kharas, M. G.
Article Title: MSI2 is required for maintaining activated myelodysplastic syndrome stem cells
Abstract: 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.
Keywords: mus
Journal Title: Nature Communications
Volume: 7
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2016-02-22
Start Page: 10739
Language: English
DOI: 10.1038/ncomms10739
PROVIDER: scopus
PMCID: PMC4764878
PUBMED: 26898884
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Virginia Klimek
    132 Klimek
  2. Haiming Xu
    18 Xu
  3. Christina Leslie
    141 Leslie
  4. Ly P Vu
    31 Vu
  5. Minal A Patel
    62 Patel
  6. Patrick Edward Tivnan
    10 Tivnan
  7. Michael Kharas
    66 Kharas
  8. Sun Mi Park
    18 Park
  9. Trevor Stephen Barlowe
    11 Barlowe
  10. James Christopher Taggart
    12 Taggart
  11. Alexandar Reinaldo Perez
    12 Perez
  12. Benjamin Heath Durham
    84 Durham
  13. Tzu Chieh   Ho
    5 Ho
  14. Rachel Owens Okabe
    2 Okabe
  15. Arthur W Chow
    13 Chow
  16. Camila Prieto
    7 Prieto