title: Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
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).
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. mkharas@partners.org
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kharas
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lengner
authors.forename: Fatima
authors.initials: F
authors.lastname: Al-Shahrour
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Brian
authors.initials: B
authors.lastname: Ball
authors.forename: Samir
authors.initials: S
authors.lastname: Zaidi
authors.forename: Kelly
authors.initials: K
authors.lastname: Morgan
authors.forename: Winnie
authors.initials: W
authors.lastname: Tam
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Paktinat
authors.forename: Rachel
authors.initials: R
authors.lastname: Okabe
authors.forename: Maricel
authors.initials: M
authors.lastname: Gozo
authors.forename: William
authors.initials: W
authors.lastname: Einhorn
authors.forename: Steven W
authors.initials: SW
authors.lastname: Lane
authors.forename: Claudia
authors.initials: C
authors.lastname: Scholl
authors.forename: Stefan
authors.initials: S
authors.lastname: Fröhling
authors.forename: Mark
authors.initials: M
authors.lastname: Fleming
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C499059:Msi2h protein, mouse; D016601:RNA-Binding Proteins