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  • Vu, Ly P.Memorial Sloan-Kettering Cancer Center (author)

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

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-04-24
  • Springer Science and Business Media LLC,2017
  • 10 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:ddd9e50b-b14c-4d70-bd3a-b51784573900
  • https://lup.lub.lu.se/record/ddd9e50b-b14c-4d70-bd3a-b51784573900URI
  • https://doi.org/10.1038/ng.3854DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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 and genre

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  • Prieto, CamilaCornell University,Memorial Sloan-Kettering Cancer Center (author)
  • Amin, Elianna M.Memorial Sloan-Kettering Cancer Center (author)
  • Chhangawala, SagarMemorial Sloan-Kettering Cancer Center,Cornell University (author)
  • Krivtsov, AndreiMemorial Sloan-Kettering Cancer Center,Harvard Medical School (author)
  • Calvo-Vidal, M. NievesWeill Cornell Medical College (author)
  • Chou, TimothyMemorial Sloan-Kettering Cancer Center (author)
  • Chow, ArthurMemorial Sloan-Kettering Cancer Center (author)
  • Minuesa, GerardMemorial Sloan-Kettering Cancer Center (author)
  • Park, Sun MiMemorial Sloan-Kettering Cancer Center (author)
  • Barlowe, Trevor S.Memorial Sloan-Kettering Cancer Center (author)
  • Taggart, JamesMemorial Sloan-Kettering Cancer Center (author)
  • Tivnan, PatrickMemorial Sloan-Kettering Cancer Center (author)
  • Deering, Raquel P.Harvard Medical School (author)
  • Chu, Lisa P.Brigham and Women's Hospital / Harvard Medical School (author)
  • Kwon, Jeong AhWhitehead Institute for Biomedical Research (author)
  • Meydan, CemWeill Cornell Medical College (author)
  • Perales-Paton, JavierSpanish National Cancer Research Center (CNIO) (author)
  • Arshi, AroraMemorial Sloan-Kettering Cancer Center (author)
  • Gönen, MithatMemorial Sloan-Kettering Cancer Center (author)
  • Famulare, ChristopherMemorial Sloan-Kettering Cancer Center (author)
  • Patel, MinalMemorial Sloan-Kettering Cancer Center (author)
  • Paietta, ElisabethMontefiore Medical Center (author)
  • Tallman, Martin S.Memorial Sloan-Kettering Cancer Center (author)
  • Lu, YuhengMemorial Sloan-Kettering Cancer Center (author)
  • Glass, JacobMemorial Sloan-Kettering Cancer Center (author)
  • Garret-Bakelman, Francine E.University of Virginia,Weill Cornell Medical College (author)
  • Melnick, AriWeill Cornell Medical College (author)
  • Levine, Ross L.Memorial Sloan-Kettering Cancer Center (author)
  • Al-Shahrour, FatimaSpanish National Cancer Research Center (CNIO) (author)
  • Järås, MarcusLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-mn8 (author)
  • Hacohen, NirHarvard Medical School (author)
  • Hwang, AlexiaMemorial Sloan-Kettering Cancer Center (author)
  • Garippa, RalphMemorial Sloan-Kettering Cancer Center (author)
  • Lengner, Christopher J.University of Pennsylvania (author)
  • Armstrong, Scott A.Harvard Medical School,Memorial Sloan-Kettering Cancer Center (author)
  • Cerchietti, LeandroHarvard Medical School (author)
  • Cowley, Glenn S.Janssen Pharmaceuticals, US (author)
  • Root, David E.Broad Institute (author)
  • Doench, JohnBroad Institute (author)
  • Leslie, ChristinaMemorial Sloan-Kettering Cancer Center (author)
  • Ebert, Benjamin L.Brigham and Women's Hospital / Harvard Medical School (author)
  • Kharas, Michael G.Memorial Sloan-Kettering Cancer Center (author)
  • Memorial Sloan-Kettering Cancer CenterCornell University (creator_code:org_t)

Related titles

  • In:Nature Genetics: Springer Science and Business Media LLC49:6, s. 866-8751061-40361546-1718

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