Novel human polyomaviruses, Merkel cell polyomavirus and human polyomavirus 9, in Japanese chronic lymphocytic leukemia cases

Abstract

BackgroundChronic 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.FindingsWe 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.ConclusionsThis 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.

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study

“…A lack of association of MCPyV with CLL is consistent with the low DNA and LT-Ag presence in CLL subjects (Shuda et al, 2009;Toracchio et al, 2009;Teman et al, 2011;Comar et al, 2012;Imajoh et al, 2012;Cimino et al, 2013), but a plausible explanation is needed for the previous findings encouraging an association (Haugg et al, 2011;Pantulu et al, 2010). The mutated sequence of MCPyV LT-Ag in the nucleus of CLL cells was only detected in six (8 %) out of 70 samples previously purified to contain mainly CD19 + /CD5 CLL cells.…”

“…Interestingly, Merkel cell carcinoma incidence has been reported to be higher among CLL patients and vice versa (Koljonen et al, 2009), suggesting a shared aetiology, although previous findings on the potential role of MCPyV in CLL have shown opposing results. The overall low prevalences (2-36 %) of viral DNA and large T-antigen (LT-Ag) detected in tumour tissue or peripheral blood mononuclear cells of CLL subjects (Shuda et al, 2009;Toracchio et al, 2009;Teman et al, 2011;Comar et al, 2012;Imajoh et al, 2012;Cimino et al, 2013) do not support an aetiological role. However, the presence of a truncated LT-Ag MCPyV sequence in the nucleus, a peculiarity of MCPyV in Merkel cell carcinoma cells, has been reported in highly purified CD19 + /CD5 + CLL cells (Haugg et al, 2011;Pantulu et al, 2010).…”

Absence of Merkel Cell Polyomavirus in Monocytic Leukemias

“…Among patients with lymphoproliferative disorders, patients with chronic lymphocytic leukemia (CLL), the most common leukemia of adults in the Western world, have higher MCPyV DNA detection rates [4]. Although most CLL tumors are not positive for MCPyV and the viral load is low, MCPyV may contribute to a significant proportion of CLL cases [6,7,8,9,10]. Our report is the first from the Eastern world to show the presence of MCPyV in a small number of Japanese CLL cases [8].…”

Involvement of Merkel Cell Polyomavirus in the Etiology and Pathogenesis of Merkel Cell Carcinoma: A Systematic Review

“…There is a correlation between the MCC and other malignancies, especially in the skin [42], highlighting the squamous cell carcinoma (SCC) [48,49], basal cell carcinoma (BCC) [48,50], and chronic lymphocytic leukemia (CLL) [51], which lead to risk of developing MCC as a secondary cancer, and vice-versa. There are other types of cancers associated with MCC, although with less number of records, making it difficult to consolidate data [52 -55].…”