Daibata Masanori, Taguchi Takahiro, Nemoto Yuiko, Iwasaki Shinji, Ohtsuki Yuji, Taguchi Hirokuni
Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan.
Int J Cancer. 2006 Jan 15;118(2):513-7. doi: 10.1002/ijc.21348.
We herein describe splenic lymphoma with villous lymphocytes (SLVL) carrying t(9;14)(p13;q32). The t(9;14)(p13;q32) is a rare reciprocal chromosome translocation found in a subset of B-cell malignancies, mainly in low-grade non-Hodgkin's lymphomas. In t(9;14)(p13;q32), PAX-5 gene on 9p13 is involved with the immunoglobulin heavy-chain gene on 14q32. It has been thought that the deregulated expression of PAX-5 as a result of t(9;14)(p13;q32) may contribute to abnormal cell proliferation. Although continuous cell lines are invaluable tools for studying lymphomagenesis in the t(9;14)(p13;q32)-bearing lymphomas, establishment of such cell lines is extremely difficult since they are usually mature B-cell malignancies. In an attempt to transform the SLVL cells into a proliferating cell line, we examined the responses of the cells to infection by Epstein-Barr virus (EBV). SLVL cells were found to be susceptible to immortalization by EBV, resulting in a permanent cell line. The cell line, designated SL-15, possessed the t(9;14)(p13;q32). Genotype analysis and immunophenotype profiles confirmed that the cell line arose from the primary lymphoma cells. The cells had characteristic cytoplasmic villi. SL-15 cells has been growing over 2 years equivalent to 350-400 population doubling levels without proliferative crisis that is often observed in EBV-positive lymphoblastoid cell lines. Furthermore, SL-15 cells, when inoculated into nude mice, formed t(9;14)(p13;q32)-bearing tumors with cytoplasmic villi. The validated SLVL-derived cell line provide a useful model system to study molecular biology of t(9;14)(p13;q32)-bearing B-cell malignancies as well as lymphomagenesis of SLVL in vitro and in vivo.
我们在此描述携带t(9;14)(p13;q32)的绒毛淋巴细胞性脾淋巴瘤(SLVL)。t(9;14)(p13;q32)是一种罕见的相互染色体易位,见于一部分B细胞恶性肿瘤,主要是低度非霍奇金淋巴瘤。在t(9;14)(p13;q32)中,9p13上的PAX-5基因与14q32上的免疫球蛋白重链基因相关。据认为,t(9;14)(p13;q32)导致的PAX-5表达失调可能促成细胞异常增殖。尽管连续细胞系是研究携带t(9;14)(p13;q32)的淋巴瘤发生机制的宝贵工具,但建立此类细胞系极其困难,因为它们通常是成熟B细胞恶性肿瘤。为了将SLVL细胞转化为增殖细胞系,我们检测了这些细胞对爱泼斯坦-巴尔病毒(EBV)感染的反应。发现SLVL细胞易被EBV永生化,从而产生一个永久细胞系。该细胞系命名为SL-15,具有t(9;14)(p13;q32)。基因型分析和免疫表型谱证实该细胞系源自原发性淋巴瘤细胞。这些细胞具有特征性的胞质绒毛。SL-15细胞已生长超过2年,相当于350 - 400个群体倍增水平,未出现EBV阳性淋巴母细胞系中常观察到的增殖危机。此外,SL-15细胞接种到裸鼠体内时,会形成带有胞质绒毛的携带t(9;14)(p13;q32)的肿瘤。经过验证的源自SLVL的细胞系为研究携带t(9;14)(p13;q32)的B细胞恶性肿瘤的分子生物学以及SLVL在体内外的淋巴瘤发生机制提供了一个有用的模型系统。