Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia

Kharas, Michael G., Lengner, Christopher J., Al-Shahrour, Fatima, Bullinger, Lars, Ball, Brian, Zaidi, Samir, Morgan, Kelly, Tam, Winnie, Paktinat, Mahnaz, Okabe, Rachel, Gozo, Maricel, Einhorn, William, Lane, Steven W., Scholl, Claudia, Froehling, Stefan, Fleming, Mark, Ebert, Benjamin L., Gilliland, D. Gary, Jaenisch, Rudolf and Daley, George Q. (2010) Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nature Medicine, 16 8: 903-908. doi:10.1038/nm.2187


Author Kharas, Michael G.
Lengner, Christopher J.
Al-Shahrour, Fatima
Bullinger, Lars
Ball, Brian
Zaidi, Samir
Morgan, Kelly
Tam, Winnie
Paktinat, Mahnaz
Okabe, Rachel
Gozo, Maricel
Einhorn, William
Lane, Steven W.
Scholl, Claudia
Froehling, Stefan
Fleming, Mark
Ebert, Benjamin L.
Gilliland, D. Gary
Jaenisch, Rudolf
Daley, George Q.
Title Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia
Journal name Nature Medicine   Check publisher's open access policy
ISSN 1078-8956
1546-170X
Publication date 2010-08
Sub-type Article (original research)
DOI 10.1038/nm.2187
Volume 16
Issue 8
Start page 903
End page 908
Total pages 7
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Formatted abstract
RNA-binding proteins of the Musashi (Msi) family are expressed in stem cell compartments and in aggressive tumors, but they have not yet been widely explored in the blood. Here we demonstrate that Msi2 is the predominant form expressed in  hematopoietic stem cells (HSCs), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of human MSI2 in a mouse model increases HSC cell cycle progression and cooperates with the chronic myeloid leukemia–associated BCR-ABL1 oncoprotein to induce an aggressive leukemia. MSI2 is overexpressed in human myeloid leukemia cell lines, and its depletion leads to decreased proliferation and increased apoptosis. Expression levels in human myeloid leukemia directly correlate with decreased survival in patients with the disease, thereby defining MSI2 expression as a new prognostic marker and as a new target for therapy in acute myeloid leukemia (AML).
Keyword Rna-Binding Protein
Oncogenic Pathway Signatures
Stem-Cells
Gene-Expression
Therapeutic-Efficacy
Human Cancer
Progenitor
Transformation
Differentiation
Progression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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