Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia
Author(s)
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 S.; Lane, Steven W.; Scholl, Claudia; Frohling, Stefan; Fleming, Mark; Ebert, Benjamin L.; Gilliland, D. Gary; Jaenisch, Rudolf; Daley, George Q.; ... Show more Show less
DownloadJaenisch_Musashi-2 regulates.pdf (766.8Kb)
OPEN_ACCESS_POLICY
Open Access Policy
Creative Commons Attribution-Noncommercial-Share Alike
Terms of use
Metadata
Show full item recordAbstract
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).
Description
available in PMC 2011 May 10.
Date issued
2010-07Department
Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical ResearchJournal
Nature Medicine
Publisher
Nature Publishing Group
Citation
Kharas, Michael G. et al. “Musashi-2 Regulates Normal Hematopoiesis and Promotes Aggressive Myeloid Leukemia.” Nature Medicine 16.8 (2010): 903–908. Web.
Version: Author's final manuscript
ISSN
1078-8956
1744-7933