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IRF4 addiction in multiple myeloma

Author

Listed:
  • Arthur L. Shaffer

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • N. C. Tolga Emre

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Laurence Lamy

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Vu N. Ngo

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • George Wright

    (Biometric Research Branch, National Cancer Institute, Rockville, Maryland 20892, USA)

  • Wenming Xiao

    (Bioinformatics and Molecular Analysis Section, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • John Powell

    (Bioinformatics and Molecular Analysis Section, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Sandeep Dave

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Xin Yu

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Hong Zhao

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Yuxin Zeng

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72212, USA)

  • Bangzheng Chen

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72212, USA)

  • Joshua Epstein

    (Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72212, USA)

  • Louis M. Staudt

    (Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

Abstract

IRF4 dependency in myeloma cells An RNA interference scan for genes linked to the proliferation of myeloma cell lines as possible drug targets has identified the transcription factor factor IRF4, needed for lymphocyte activation and plasma cell differentiation in normal cells, as a master regulator of multiple myeloma. Strikingly, myeloma cells are completely dependent on IRF4, despite that fact that most do not harbour mutations, translocations or amplifications of the IRF4 locus. In cancer cells, IRF4 controls a different network of genes — including the MYC oncogene — than in normal plasma cells or activated B cells. IRF4 dependency in myeloma is an example of 'non-oncogene addiction', where cancer cells depend on a normal cellular protein for proliferation and/or survival.

Suggested Citation

  • Arthur L. Shaffer & N. C. Tolga Emre & Laurence Lamy & Vu N. Ngo & George Wright & Wenming Xiao & John Powell & Sandeep Dave & Xin Yu & Hong Zhao & Yuxin Zeng & Bangzheng Chen & Joshua Epstein & Louis, 2008. "IRF4 addiction in multiple myeloma," Nature, Nature, vol. 454(7201), pages 226-231, July.
    • Handle: RePEc:nat:nature:v:454:y:2008:i:7201:d:10.1038_nature07064
    DOI: 10.1038/nature07064
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    Cited by:

    1. Stella Amanda & Tze King Tan & Jolynn Zu Lin Ong & Madelaine Skolastika Theardy & Regina Wan Ju Wong & Xiao Zi Huang & Muhammad Zulfaqar Ali & Yan Li & Zhiyuan Gong & Hiroshi Inagaki & Ee Yong Foo & B, 2022. "IRF4 drives clonal evolution and lineage choice in a zebrafish model of T-cell lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Nikolai Schleussner & Pierre Cauchy & Vedran Franke & Maciej Giefing & Oriol Fornes & Naveen Vankadari & Salam A. Assi & Mariantonia Costanza & Marc A. Weniger & Altuna Akalin & Ioannis Anagnostopoulo, 2023. "Transcriptional reprogramming by mutated IRF4 in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Yandan Yang & Arnold Bolomsky & Thomas Oellerich & Ping Chen & Michele Ceribelli & Björn Häupl & George W. Wright & James D. Phelan & Da Wei Huang & James W. Lord & Callie K. Winkle & Xin Yu & Jan Wis, 2022. "Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Yuen Lam Dora Ng & Evelyn Ramberger & Stephan R. Bohl & Anna Dolnik & Christian Steinebach & Theresia Conrad & Sina Müller & Oliver Popp & Miriam Kull & Mohamed Haji & Michael Gütschow & Hartmut Döhne, 2022. "Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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