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Lymphoma

Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas

Leukemia volume 23, pages 574–580 (2009)Cite this article

Abstract

Oncogenes involved in recurrent chromosomal translocations serve as diagnostic markers and therapeutic targets in hematopoietic tumors. In contrast to myeloid and B-cell neoplasms, translocations in peripheral T-cell lymphomas (PTCLs) are poorly understood. Here, we identified recurrent translocations involving the multiple myeloma oncogene-1/interferon regulatory factor-4 (IRF4) locus in PTCLs. IRF4 translocations exist in myeloma and some B-cell lymphomas, but have not been reported earlier in PTCLs. We studied 169 PTCLs using fluorescence in situ hybridization and identified 12 cases with IRF4 translocations. Two cases with t(6;14)(p25;q11.2) had translocations between IRF4 and the T-cell receptor-alpha (TCRA) locus. Both were cytotoxic PTCLs, unspecified (PTCL-Us) involving bone marrow and skin. In total, 8 of the remaining 10 cases were cutaneous anaplastic large-cell lymphomas (ALCLs) without TCRA rearrangements (57% of cutaneous ALCLs tested). These findings identified IRF4 translocations as a novel recurrent genetic abnormality in PTCLs. Cytotoxic PTCL-Us involving bone marrow and skin and containing IRF4/TCRA translocations might represent a distinct clinicopathologic entity. Translocations involving IRF4 but not TCRA appear to occur predominantly in cutaneous ALCLs. Detecting these translocations may be useful in lymphoma diagnosis. Further, due to its involvement in translocations, MUM1/IRF4 protein may play an important biologic role in some PTCLs, and might represent a possible therapeutic target.

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Acknowledgements

This study was supported in part by a Career Development Award (to ALF) from the Iowa/Mayo Lymphoma SPORE (P50 CA97274) and part of the study was presented at the 97th Annual Meeting of the United States and Canadian Academy of Pathology on 4 March 2008. We gratefully acknowledge Ms Monica Kramer for her excellent secretarial support.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    A L Feldman, M Law, E D Remstein, W R Macon, L A Erickson, K L Grogg, P J Kurtin & A Dogan

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  1. A L Feldman
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Correspondence to A L Feldman.

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Feldman, A., Law, M., Remstein, E. et al. Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 23, 574–580 (2009). https://doi.org/10.1038/leu.2008.320

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