MSI2 is required for maintaining activated myelodysplastic syndrome stem cells

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

来源：Nature Communications, 2016, 7(1): 10739.

DOI：10.1038/ncomms10739

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.

• 出版日期2016-2