MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies
MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies
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DOI：
10.1038/sj.leu.2401696
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发表时间：
2000-03-01
期刊：
影响因子：
11.4
通讯作者：
Ueda, R
中科院分区：
文献类型：
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作者：
Tsuboi, K;Iida, S;Ueda, R
MUM1/IRF4是一种骨髓瘤相关的癌基因，由于t(6;14)(p25,q32)染色体易位以及因其与免疫球蛋白重链基因（IgH）位点并置而被转录激活。当该癌基因失去功能时，未观察到活化的B/T淋巴细胞和分泌Ig的浆细胞，这表明MUM1/IRF4对淋巴样发育至关重要。通过使用针对MUM1/IRF4的特异性山羊抗血清的免疫组织化学技术，在反应性淋巴组织和淋巴瘤组织中对其表达进行了分析。该分析检测到一种50kDa的MUM1产物，其定位局限于淋巴细胞的细胞核。发现反应性淋巴结中的MUM1(+)细胞由浆细胞和一小部分（约7.9%）携带CD20(+)CD38(+)的B细胞组成，这些细胞位于生发中心的亮区。有丝分裂原刺激会上调外周血B/T淋巴细胞中的MUM1表达，这表明MUM1阳性代表B/T细胞的活化状态。在B细胞非霍奇金淋巴瘤（NHL）中，在73.2%（30/41）的弥漫性大B细胞淋巴瘤（DLBCL）、20%（1/5）的边缘区淋巴瘤（MZL）和43%（3/7）的小淋巴细胞淋巴瘤（SLL）病例中观察到MUM1表达，而在任何套细胞淋巴瘤（MCL）或滤泡中心淋巴瘤（FCL）病例中均未观察到。此外，在包括成人T细胞白血病/淋巴瘤（ATL/L）和间变性大细胞淋巴瘤（ALCL）在内的各种类型的T细胞淋巴瘤以及大多数霍奇金病中，MUM1呈高强度染色。我们的结果表明，大部分淋巴瘤由表达MUM1蛋白的生理上或异常活化的肿瘤性淋巴细胞组成。
MUM1/IRF4 is a myeloma-associated oncogene transcriptionally activated as a result of t(6;14)(p25,q32) chromosomal translocation and by virtue of its juxtaposition to the immunoglobulin heavy chain gene (IgH) locus. When this oncogene becomes non-functional, no activated B/T lymphocytes and lg secreting plasma cells are observed, suggesting that MUM1/IRF4 is crucial for lymphoid development. Its expression was analyzed in both reactive lymphoid and lymphoma tissues by means of an immunohistochemical technique using specific goat antiserum against MUM1/IRF4. This analysis detected a 50 kDa MUM1 product whose localization was restricted to the nuclei of the lymphocytes. The MUM1(+) cells in reactive lymph nodes were found to consist of plasma cells and a small fraction (approximately 7.9%) of B cells harboring CD20(+)CD38(+), which were located in the light zone of the germinal center. MUM1 expression in peripheral blood B/T lymphocytes was upregulated by mitogenic stimuli, suggesting that MUM1 positivity represents the activated state of the B/T cells. In B cell non-Hodgkin's lymphoma (NHL), MUM1 expression was observed in 73.2% (30/41) of diffuse large B cell lymphoma (DLBCL), 20% (1/5) of marginal zone lymphoma (MZL) and 43% (3/7) of small lymphocytic lymphoma (SLL) cases, whereas it was not seen in any cases of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL), Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases. Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.