Feldman A L, Law M, Remstein E D, Macon W R, Erickson L A, Grogg K L, Kurtin P J, Dogan A
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Leukemia. 2009 Mar;23(3):574-80. doi: 10.1038/leu.2008.320. Epub 2008 Nov 6.
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.
参与复发性染色体易位的癌基因可作为造血系统肿瘤的诊断标志物和治疗靶点。与髓系和B细胞肿瘤不同，外周T细胞淋巴瘤（PTCL）中的易位情况尚不清楚。在此，我们在PTCL中鉴定出涉及多发性骨髓瘤癌基因-1/干扰素调节因子-4（IRF4）基因座的复发性易位。IRF4易位存在于骨髓瘤和一些B细胞淋巴瘤中，但此前在PTCL中尚未见报道。我们使用荧光原位杂交技术研究了169例PTCL，鉴定出12例存在IRF4易位。2例t(6;14)(p25;q11.2)患者的IRF4与T细胞受体α（TCRA）基因座之间发生了易位。二者均为细胞毒性未特指的PTCL（PTCL-U），累及骨髓和皮肤。其余10例中共有8例为无TCRA重排的皮肤间变性大细胞淋巴瘤（ALCL）（占检测的皮肤ALCL的57%）。这些发现确定IRF4易位是PTCL中一种新的复发性基因异常。累及骨髓和皮肤且含有IRF4/TCRA易位的细胞毒性PTCL-U可能代表一种独特的临床病理实体。涉及IRF4但不涉及TCRA的易位似乎主要发生在皮肤ALCL中。检测这些易位可能有助于淋巴瘤的诊断。此外，由于MUM1/IRF4蛋白参与易位，它可能在某些PTCL中发挥重要的生物学作用，并可能代表一个潜在的治疗靶点。
