Department of Microbiology and Infection, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
J Hematol Oncol. 2012 Jun 1;5:25. doi: 10.1186/1756-8722-5-25.
Chronic lymphocytic leukemia (CLL) is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV) and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9), another lymphotropic polyomavirus, in Japanese CLL cases.
We found that 9/27 CLL cases (33.3 %) were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT) gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST) gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350.
This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.
慢性淋巴细胞白血病(CLL)在日本是最罕见的成人白血病,而在西方国家则是最常见的白血病。来自美国和德国的最近研究表明,Merkel 细胞多瘤病毒(MCPyV)与 CLL 之间可能存在病因关联,尽管来自东方国家的数据尚未报道。为了增加相关数据量,本研究调查了日本 CLL 病例中 MCPyV 和另一种淋巴嗜性多瘤病毒人多瘤病毒 9(HPyV9)的流行率和 DNA 载量。
我们使用定量实时聚合酶链反应分析发现,27 例 CLL 病例中有 9 例(33.3%)为 MCPyV 阳性。病毒 DNA 载量范围为 0.000017 至 0.0012 个拷贝/细胞。所有病例均为 HPyV9 阴性。对一个 MCPyV 阳性的 CLL 病例进行了大 T(LT)基因的突变分析,结果表明存在野生型 MCPyV,没有核苷酸缺失。对整个小 T(ST)基因和部分 LT 基因的 DNA 序列分析表明,与北美分离株 MCC350 的参考序列相比,日本的 MCPyV 分离株 CLL-JK 有两个核苷酸缺失。
本研究首次提供证据表明,MCPyV 存在于具有低病毒 DNA 载量的日本 CLL 病例亚群中。MCPyV 和 HPyV9 不太可能直接导致大多数日本病例的 CLL 发展。从日本 CLL 病例中分离出的 MCPyV 可能构成一个亚洲群,其致病性需要在未来的研究中阐明。