Amini Rose-Marie, Berglund Mattias, Rosenquist Richard, Von Heideman Anne, Lagercrantz Svetlana, Thunberg Ulf, Bergh Jonas, Sundström Christer, Glimelius Bengt, Enblad Gunilla
Department of Genetics and Pathology, Uppsala University, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
Leuk Lymphoma. 2002 Nov;43(11):2179-89. doi: 10.1080/1042819021000032917.
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.
对于接受霍奇金淋巴瘤（HL）治疗的患者发生继发性非霍奇金淋巴瘤（NHL）的机制，人们了解甚少。我们的目的是详细表征一株源自弥漫性大B细胞淋巴瘤（DLBCL）的细胞系，该淋巴瘤发生于一名复发性HL患者。细胞系U - 2932是从一名曾接受多种化疗方案治疗HL的DLBCL患者的腹水中建立的。表征基于形态学、免疫表型、爱泼斯坦 - 巴尔病毒（EBV）状态、IgH基因重排状态、致瘤性、p53测序以及p53、BCL - 2和BCL - 6的免疫组化表达。使用G显带、比较基因组杂交（CGH）和光谱核型分析（SKY）研究核型。该细胞系表现出DLBCL的典型形态特征，并在裸鼠中形成集落生长。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。通过证明患者腹水中存在相同的V(H)4重排，证实了U - 2932的起源。在第１７６位氨基酸处检测到肿瘤抑制基因p53的点突变，并且还证实了p53蛋白的免疫组化过表达。U - 2932具有复杂的核型，包括染色体带18q21和3q27的高水平扩增，并在免疫组化中表达异常的BCL - 2和BCL - 6。我们无法研究原始HL与U - 2932之间的克隆关系。总之，U - 2932是一株从患有HL继而发生NHL的患者中建立的独特B细胞系。BCL - 2、BCL - 6和p53的过表达可能在肿瘤发生和耐药性中起作用。该细胞系可能成为一个有用的工具，以更好地理解HL治疗患者中继发性NHL发生的机制。
