The Feinstein Institute for Medical Research, North Shore-Long Island Jewish-LIJ Health System, Manhasset, New York, United States of America.
Mol Med. 2011;17(11-12):1338-48. doi: 10.2119/molmed.2010.00110. Epub 2011 Sep 21.
An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility. Using genome amplification methods, we identified a new isolate (BIS8-17) of torque teno virus (TTV) 10. The presence of blood isolate sequence 8-17 (BIS8-17) in the original plasma was confirmed by polymerase chain reaction (PCR), validating the approach, since TTV is a known plasma virus. Subsequent PCR testing of plasmas from additional patients showed that BIS8-17 had a similar incidence (~20%) in CLL (n = 48) or PV (n = 10) compared with healthy controls (n = 52). CLL cells do not harbor BIS8-17; PCR did not detect it in CLL peripheral blood genomic deoxyribonucleic acid (DNA) (n = 20). CLL patient clinical outcome or prognostic markers (immunoglobulin heavy chain variable region [IGHV ] mutation, CD38 or zeta-chain associated protein kinase 70 kDa [ZAP-70]) did not correlate with BIS8-17 infection. Although not causative to our knowledge, this is the first reported isolation and detection of TTV in either CLL or PV. TTV could serve as a covirus with another infectious agent or TTV variant with rearranged genetic components that contribute to disease pathogenesis. These results prove that this method identifies infectious agents and provides an experimental methodology to test correlation with disease.
已经提出了许多人类癌症的感染病因,但很少能确定具体的病原体。一个困难是需要在体外繁殖癌细胞,以产生可检测数量的感染剂。我们假设可以适应从少量细胞中进行基因组扩增来规避这一困难。一位同时患有慢性淋巴细胞白血病(CLL)和真性红细胞增多症(PV)的患者需要进行治疗性放血,因此捐献了大量放血后的血液来测试这种可能性。我们使用基因组扩增方法鉴定了一种新型旋毛虫病毒(TTV)10 的分离株(BIS8-17)。通过聚合酶链反应(PCR)证实了原始血浆中存在血液分离物序列 8-17(BIS8-17),从而验证了该方法的有效性,因为 TTV 是一种已知的血浆病毒。随后对来自其他患者的血浆进行 PCR 检测显示,与健康对照组(n=52)相比,BIS8-17 在 CLL(n=48)或 PV(n=10)中的发生率相似(~20%)。CLL 细胞不携带 BIS8-17;PCR 未在 CLL 外周血基因组脱氧核糖核酸(DNA)(n=20)中检测到它。CLL 患者的临床结局或预后标志物(免疫球蛋白重链可变区[IGHV]突变、CD38 或 ζ 链相关蛋白激酶 70 kDa [ZAP-70])与 BIS8-17 感染无关。尽管据我们所知,这不是致病因素,但这是首次在 CLL 或 PV 中报告 TTV 的分离和检测。TTV 可能作为另一种感染因子或具有重排遗传成分的 TTV 变体的伴随病毒,从而促进疾病的发病机制。这些结果证明了该方法可以识别感染因子,并提供了一种实验方法来测试与疾病的相关性。