• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Martinez-Soria, N
    McKenzie, L
    Draper, Julia E
    Ptasinska, A
    Issa, H
    Potluri, S
    Blair, HJ
    Pickin, A
    Isa, A
    Chin, PS
    Tirtakusuma, R
    Coleman, D
    Nakjang, S
    Assi, S
    Forster, V
    Reza, M
    Law, E
    Berry, P
    Mueller, D
    Elder, A
    Bomken, SN
    Pal, D
    Allan, JM
    Veal, GJ
    Cockerill, PN
    Wichmann, C
    Vormoor, J
    Lacaud, Georges
    Bonifer, C
    Heidenreich, O
    Show allShow less
    Affiliation
    Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Brewery Lane, Newcastle upon Tyne NE1 7RU, UK
    Issue Date
    2018
    
    Metadata
    Show full item record
    Abstract
    Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. We used epigenomic profiling data for an RNAi screen to interrogate the transcriptional network maintaining t(8;21) AML. This strategy identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO-driven leukemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug significantly impairs leukemic expansion of patient-derived AML cells and engraftment in immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO maintains leukemia by promoting cell cycle progression and identifies G1 CCND-CDK complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML.
    Citation
    Martinez-Soria N, McKenzie L, Draper J, Ptasinska A, Issa H, Potluri S, et al. The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation. Cancer Cell [Internet]. 2018 Oct;34(4):626�642.e8.
    Journal
    Cancer Cell
    URI
    http://hdl.handle.net/10541/621367
    DOI
    10.1016/j.ccell.2018.08.015
    PubMed ID
    30300583
    Additional Links
    https://dx.doi.org/10.1016/j.ccell.2018.08.015
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ccell.2018.08.015
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.
    • Authors: Ptasinska A, Pickin A, Assi SA, Chin PS, Ames L, Avellino R, Gröschel S, Delwel R, Cockerill PN, Osborne CS, Bonifer C
    • Issue date: 2019 Sep 17
    • Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding.
    • Authors: Ptasinska A, Assi SA, Mannari D, James SR, Williamson D, Dunne J, Hoogenkamp M, Wu M, Care M, McNeill H, Cauchy P, Cullen M, Tooze RM, Tenen DG, Young BD, Cockerill PN, Westhead DR, Heidenreich O, Bonifer C
    • Issue date: 2012 Aug
    • RUNX1-ETO induces a type I interferon response which negatively effects t(8;21)-induced increased self-renewal and leukemia development.
    • Authors: DeKelver RC, Lewin B, Weng S, Yan M, Biggs J, Zhang DE
    • Issue date: 2014 Apr
    • The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes.
    • Authors: Bakshi R, Zaidi SK, Pande S, Hassan MQ, Young DW, Montecino M, Lian JB, van Wijnen AJ, Stein JL, Stein GS
    • Issue date: 2008 Dec 1
    • Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling.
    • Authors: Pulikkan JA, Madera D, Xue L, Bradley P, Landrette SF, Kuo YH, Abbas S, Zhu LJ, Valk P, Castilla LH
    • Issue date: 2012 Jul 26
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.