Editor's Summary

10 July 2008

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.

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Both oncogenes and normal genes can mediate the development and progress of cancer. What used to separate their effects was cancer's dependence on, or 'addiction' to, oncogenes but not normal genes. Not any more.

John D. Shaughnessy

doi:10.1038/454172a

LetterIRF4 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 & Louis M. Staudt

doi:10.1038/nature07064