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Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells

Vu, Ly P. (author)
Memorial Sloan-Kettering Cancer Center
Prieto, Camila (author)
Cornell University,Memorial Sloan-Kettering Cancer Center
Amin, Elianna M. (author)
Memorial Sloan-Kettering Cancer Center
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Chhangawala, Sagar (author)
Memorial Sloan-Kettering Cancer Center,Cornell University
Krivtsov, Andrei (author)
Memorial Sloan-Kettering Cancer Center,Harvard Medical School
Calvo-Vidal, M. Nieves (author)
Weill Cornell Medical College
Chou, Timothy (author)
Memorial Sloan-Kettering Cancer Center
Chow, Arthur (author)
Memorial Sloan-Kettering Cancer Center
Minuesa, Gerard (author)
Memorial Sloan-Kettering Cancer Center
Park, Sun Mi (author)
Memorial Sloan-Kettering Cancer Center
Barlowe, Trevor S. (author)
Memorial Sloan-Kettering Cancer Center
Taggart, James (author)
Memorial Sloan-Kettering Cancer Center
Tivnan, Patrick (author)
Memorial Sloan-Kettering Cancer Center
Deering, Raquel P. (author)
Harvard Medical School
Chu, Lisa P. (author)
Brigham and Women's Hospital / Harvard Medical School
Kwon, Jeong Ah (author)
Whitehead Institute for Biomedical Research
Meydan, Cem (author)
Weill Cornell Medical College
Perales-Paton, Javier (author)
Spanish National Cancer Research Center (CNIO)
Arshi, Arora (author)
Memorial Sloan-Kettering Cancer Center
Gönen, Mithat (author)
Memorial Sloan-Kettering Cancer Center
Famulare, Christopher (author)
Memorial Sloan-Kettering Cancer Center
Patel, Minal (author)
Memorial Sloan-Kettering Cancer Center
Paietta, Elisabeth (author)
Montefiore Medical Center
Tallman, Martin S. (author)
Memorial Sloan-Kettering Cancer Center
Lu, Yuheng (author)
Memorial Sloan-Kettering Cancer Center
Glass, Jacob (author)
Memorial Sloan-Kettering Cancer Center
Garret-Bakelman, Francine E. (author)
University of Virginia,Weill Cornell Medical College
Melnick, Ari (author)
Weill Cornell Medical College
Levine, Ross L. (author)
Memorial Sloan-Kettering Cancer Center
Al-Shahrour, Fatima (author)
Spanish National Cancer Research Center (CNIO)
Järås, Marcus (author)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine
Hacohen, Nir (author)
Harvard Medical School
Hwang, Alexia (author)
Memorial Sloan-Kettering Cancer Center
Garippa, Ralph (author)
Memorial Sloan-Kettering Cancer Center
Lengner, Christopher J. (author)
University of Pennsylvania
Armstrong, Scott A. (author)
Harvard Medical School,Memorial Sloan-Kettering Cancer Center
Cerchietti, Leandro (author)
Harvard Medical School
Cowley, Glenn S. (author)
Janssen Pharmaceuticals, US
Root, David E. (author)
Broad Institute
Doench, John (author)
Broad Institute
Leslie, Christina (author)
Memorial Sloan-Kettering Cancer Center
Ebert, Benjamin L. (author)
Brigham and Women's Hospital / Harvard Medical School
Kharas, Michael G. (author)
Memorial Sloan-Kettering Cancer Center
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 (creator_code:org_t)
2017-04-24
2017
English 10 s.
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:6, s. 866-875
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis. Gene expression profiling of SYNCRIP-depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets. SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion. Altogether, our data identify SYNCRIP as a new RBP that controls the myeloid leukemia stem cell program. We propose that targeting these RBP complexes might provide a novel therapeutic strategy in leukemia.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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