Nakamura Naoya, Nakamura Shigeo, Yamaguchi Motoko, Ichinohasama Ryo, Yoshino Tadashi, Kuze Tetsuo, Sasaki Yoshikazu, Yoshida Sachiko, Abe Masafumi
Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Int J Hematol. 2005 Jan;81(1):58-61. doi: 10.1532/ijh97.04119.
CD5+ diffuse large B-cell lymphoma (DLBCL) has recently been identified as a subgroup with different clinical characteristics from CD5- DLBCL and as having a poorer outcome than CD5- DLBCL. Data regarding differences in gene alteration between CD5+ and CD5- DLBCL have accumulated. In this article, we report an analysis of the immunoglobulin heavy-chain gene variable region (VH) gene in 35 cases of CD5+ DLBCL and compare these cases with those with the germline of the VH gene (GL-VH) and those with a somatically hypermutated VH gene (HM-VH). When the CD5+ DLBCL cases were subdivided with a cutoff value of 98% homology in the VH gene, there were 7 cases (20%) of GL-VH and 28 cases (80%) of HM-VH. The proportion of GL-VH cases in CD5+ DLBCL was more than that in CD5 DLBCL. Although we found no significant difference in pretreatment clinical parameters between the GL-VH and HM-VH subgroups, there was a tendency for the GL-VH subgroup to show lower incidences of elevation of lactate dehydrogenase and >1 site of extranodal involvement compared to the HM-VH subgroup. The overall survival curve of the HM-VH subgroup showed a rapid decline followed by a plateau, whereas that of the GL-VH subgroup declined constantly after 5 years, suggesting that GL-VH disease may not be curable by standard therapies. These findings suggest that CD5+ DLBCL with GL-VH shares clinical features with mantle cell lymphoma, the cellular origin of which has been considered to be pre-germinal center B-cells. We therefore propose that analysis of the VH gene is important for predicting the clinical course of CD5+ DLBCL.
CD5+弥漫性大B细胞淋巴瘤（DLBCL）最近被确定为一个具有与CD5- DLBCL不同临床特征的亚组，且其预后比CD5- DLBCL更差。关于CD5+和CD5- DLBCL之间基因改变差异的数据已经积累。在本文中，我们报告了对35例CD5+ DLBCL免疫球蛋白重链基因可变区（VH）基因的分析，并将这些病例与VH基因种系（GL-VH）和体细胞超突变VH基因（HM-VH）的病例进行比较。当CD5+ DLBCL病例以VH基因98%同源性的临界值进行细分时，则有7例（20%）为GL-VH，28例（80%）为HM-VH。CD5+ DLBCL中GL-VH病例所占比例高于CD5- DLBCL。虽然我们发现GL-VH和HM-VH亚组之间预处理临床参数无显著差异，但与HM-VH亚组相比，GL-VH亚组乳酸脱氢酶升高和结外累及>1个部位的发生率有降低趋势。HM-VH亚组的总生存曲线显示快速下降后趋于平稳，而GL-VH亚组的总生存曲线在5年后持续下降，这表明GL-VH疾病可能无法通过标准疗法治愈。这些发现表明，具有GL-VH的CD5+ DLBCL与套细胞淋巴瘤具有共同的临床特征，套细胞淋巴瘤的细胞起源被认为是生发中心前B细胞。因此，我们提出VH基因分析对于预测CD5+ DLBCL的临床病程很重要。
