A novel B-cell line (U-2932) established from a patient with diffuse large B-cell lymphoma following Hodgkin lymphoma
A novel B-cell line (U-2932) established from a patient with diffuse large B-cell lymphoma following Hodgkin lymphoma
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DOI：
10.1080/1042819021000032917
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发表时间：
2002-11-01
影响因子：
2.6
通讯作者：
Enblad, G
中科院分区：
文献类型：
--
作者：
Amini, RM;Berglund, M;Enblad, G
对于接受霍奇金淋巴瘤 (HL) 治疗的患者导致继发性非霍奇金淋巴瘤 (NHL) 的机制知之甚少。我们的目的是详细表征源自复发性 HL 患者的弥漫性大 B 细胞淋巴瘤 (DLBCL) 的细胞系。细胞系 U-2932 是从一名患有 DLBCL 的患者的腹水中建立的，该患者之前曾接受过多种化疗方案治疗 HL。表征基于形态学、免疫表型、EB 病毒 (EBV) 状态、IgH 基因重排状态、致瘤性、p53 测序以及 p53、BCL-2 和 BCL-6 的免疫组织化学表达。使用 G 带、比较基因组杂交 (CGH) 和光谱核型 (SKY) 分析研究核型。该细胞系显示出 DLBCL 的典型形态特征，并在裸鼠体内以集落形式生长。它表达具有体细胞超突变 V(H)4-39 基因的 B 细胞表型，且 EBV 呈阴性。通过在患者腹水中展示相同的 V(H)4 重排，证实了 U-2932 的来源。在氨基酸位置 176 处检测到肿瘤抑制基因 p53 的点突变，并且还证明了 p53 蛋白的免疫组织化学过度表达。 U-2932 携带复杂的核型，包括染色体带 18q21 和 3q27 的高水平扩增，并在免疫组织化学上表达异常的 BCL-2 和 BCL-6。我们无法调查原始 HL 和 U-2932 之间的克隆关系。总之，U-2932 是一种独特的 B 细胞系，是从患有 HL 随后又患有 NHL 的患者中建立的。 BCL-2、BCL-6和p53的过度表达可能在肿瘤发生和耐药性中发挥作用。该细胞系可能成为更好地了解 HL 治疗患者继发性 NHL 发展机制的有用工具。
Little is known about mechanisms leading to secondary non-Hodgkin lymphomas (NHL) in patients treated for Hodgkin lymphoma (HL). Our aim was to characterise in detail a cell line derived from a diffuse large B-cell lymphoma (DLBCL) that had developed in a patient with relapsing HL. The cell line U-2932 was established from ascites in a patient suffering from DLBCL previously treated for HL with multiple chemotherapy regimens. Characterisation was based on morphology, immunophenotype, Epstein-Barr virus (EBV)-status, IgH gene rearrangement status, tumourigenicity, p53 sequencing, and immunohistochemical expression of p53, BCL-2 and BCL-6. The karyotype was investigated using G-banding, comparative genomic hybridisation (CGH) and spectral karyotype (SKY) analysis. This cell line shows typical morphological features of a DLBCL and grows as colonies in nude mice. It expresses a B-cell phenotype with a somatically hypermutated V(H)4-39 gene and is negative for EBV. The origin of U-2932 was confirmed by demonstrating an identical V(H)4 rearrangement in ascites from the patient. A point mutation of the tumour-suppressor gene p53 was detected in amino acid position 176 and immunohistochemical over-expression of the p53 protein was also demonstrated. U-2932 carries a complex karyotype including high-level amplifications of the chromosomal bands 18q21 and 3q27 and expresses aberrant BCL-2 and BCL-6 immunohistochemically. We were unable to investigate the clonal relationship between the original HL and U-2932. In conclusion, U-2932 is a unique B cell line established from a patient suffering from HL followed by NHL. Overexpression of BCL-2, BCL-6 and p53 may play a role in the tumourigenesis and drug resistance. This cell line may become a useful tool to better understand the mechanisms responsible for development of secondary NHL in patients treated for HL.