Clonality and methylation status of the Epstein-Barr virus (EBV) genomes in in vivo-infected EBV-carrying chronic lymphocytic leukemia (CLL) cell lines.
Clonality and methylation status of the Epstein-Barr virus (EBV) genomes in in vivo-infected EBV-carrying chronic lymphocytic leukemia (CLL) cell lines.
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体内感染的携带 EBV 的慢性淋巴细胞白血病 (CLL) 细胞系中 Epstein-Barr 病毒 (EBV) 基因组的克隆性和甲基化状态。
DOI：
10.1002/ijc.2910480112
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发表时间：
1991
影响因子：
6.4
通讯作者：
Klein,E
中科院分区：
文献类型：
--
作者：
Lewin,N;Minarovits,J;Weber,G;Ehlin-Henriksson,B;Wen,T;Mellstedt,H;Klein,G;Klein,E
从慢性淋巴细胞白血病（CLL）患者（PG）中多次建立携带EB-巴尔病毒（EBV）的直接生长细胞系。这些细胞系携带与体内白血病细胞相同的环状15号染色体，并且同样是12号染色体三体。它们都显示出相同的JH重排，表明它们来自相同的B-细胞祖细胞。它们也有相同的单个EBV末端重复序列（TR），表明它们是由单个EBV感染事件产生的。可以推测，单个CLL细胞已经被EBVin体内感染，并且随后在CLL群体中建立了自身作为亚克隆。这个亚群在体内持续存在，但似乎并不随时间而扩大。在增殖后，它转化为淋巴母细胞样细胞并选择性增殖为永生化细胞系。白血病代表性CLL系与通过体外感染平行建立的患者B 95 -8病毒转化的正常二倍体细胞在表型上无法区分。它们作为典型的LCL簇生长，并表达相同的B-细胞活化标志物。EBV-DNA的甲基化状态在CLL系和B 95 -8病毒转化的LCL中不同。当用BamHI C、E、H和W片段探测Hpall和Mspl消化的DNA时，CLL系显示出甲基化和未甲基化限制性片段的混合物，如某些携带EBV的伯基特淋巴瘤（BL）系中一样。相反，B 95 -8病毒转化的正常二倍体细胞的EBV-DNA完全未甲基化，与其他LCL一样。
Directly growing Epstein‐Barr virus (EBV)‐carrying cell lines were established from a chronic lymphocytic leukemia (CLL) patient (PG) on repeated occasions. The lines carried the same ring chromosome 15 as the leukemia cellsin vivoand were similarly trisomic for chromosome 12. They all showed the same JHrearrangement, indicating that they had arisen from the same B‐cell progenitor. They also had the same single EBV‐terminal repeat (TR), indicating that they had been generated by a single EBV infection event. It may be surmised that a single CLL cell had been infected by EBVin vivoand established itself subsequently as a subclone within the CLL population. This subpopulation persistsin vivobut does not appear to expand with time. After explantation, it transforms into lymphoblastoid cells and proliferates selectively as immortalized lines. The leukemia‐representative CLL lines were phenotypically indistinguishable from the B95–8 virus‐transformed normal diploid cells of the patient, established in parallel byin vitroinfection. They grew as typical LCL clusters and expressed the same B‐cell activation markers. The methylation status of EBV‐DNA was different in the CLL lines and the B95–8‐virus‐transformed LCLs. When Hpall‐and Mspl‐ digested DNA was probed with BamHI C, E, H and W fragments, the CLL lines showed a mixture of methylated and unmethylated restriction fragments as in certain EBV‐carrying Burkitt lymphoma (BL) lines. In contrast, the EBV‐DNA of B95–8 virus‐transformed normal diploid cells was completely unmethylated, as in other LCLs.