IRF4 addiction in multiple myeloma

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 and Louis M. Staudt ()
Additional contact information
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

Nature, 2008, vol. 454, issue 7201, 226-231

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.

Date: 2008
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DOI: 10.1038/nature07064

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