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Predominant Merkel Cell Polyomavirus DNA Detection in Essential Thrombocythemia within Myeloproliferative Neoplasms
Dan Liu1,2, Sixuan J Wang3,4, Amanda Macamo1
1Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, the Netherlands.
Abstract:
Acute thrombocythemic myeloproliferative disease in mice has been reported upon introduction of middle T gene expression of mouse polyomavirus. Merkel cell polyomavirus (MCPyV) is an oncogenic human polyomavirus that accounts for approximately 80% of all Merkel cell carcinomas. In this study, we assessed the presence of MCPyV DNA in fresh bone marrow (BM) aspirates from patients with myeloproliferative neoplasms (MPN) using MCPyV-specific DNA polymerase chain reaction. MCPyV DNA prevalence was significantly higher in 78 BM samples from patients with MPNs (17.9%, 14/78) than in 66 BM controls undergoing femoral head replacement surgery (3%, 2/66; Fisher exact test, P = 0.0063; OR = 7.95% confidence interval = 1.53-32.06). Notably, positivity was predominant in essential thrombocythemia (ET; 11/14). MCPyV mRNA was detected in MCPyV DNA-positive samples, indicating low-level viral transcription. Interestingly, MCPyV positivity was significantly correlated with female sex but not with age or specific MPN genetic mutations, except for myeloproliferative leukemia virus oncogene mutations. These findings suggest a potential association between MCPyV and MPNs, particularly ET, and support further investigation into the role of human polyomavirus in megakaryocytic lineage biology.
Significance:
MCPyV DNA was detected in BM samples from patients with MPNs, especially those with ET. This observation suggests possible involvement of MCPyV in megakaryocytic lineage biology, providing new insights into MPN pathogenesis and promoting further investigation into the role of human polyomaviruses in hematologic disorders.
Insights
Merkel cell polyomavirus (MCPyV) DNA was found more often in bone marrow of myeloproliferative neoplasm (MPN) patients, especially essential thrombocythemia (ET). This suggests a possible link between MCPyV and MPNs.
Area of Science:
- Oncology
- Virology
- Hematology
Background:
- Merkel cell polyomavirus (MCPyV) is an oncogenic human polyomavirus linked to Merkel cell carcinoma.
- Mouse polyomavirus Middle T gene expression induces acute thrombocythemic myeloproliferative disease in mice.
- Myeloproliferative neoplasms (MPNs) are a group of diseases characterized by the overproduction of myeloid cells.
Purpose of the Study:
- To investigate the presence of MCPyV DNA in bone marrow (BM) aspirates from patients with MPNs.
- To explore the potential association between MCPyV and MPNs, particularly essential thrombocythemia (ET).
Main Methods:
- MCPyV-specific DNA polymerase chain reaction (PCR) was used to detect MCPyV DNA in 78 MPN patient BM samples and 66 control BM samples.
- MCPyV mRNA detection was performed in MCPyV-DNA-positive samples to assess viral transcription.
- Statistical analyses, including Fisher's exact test, were employed to compare MCPyV prevalence between MPN patients and controls and to identify correlations.
Main Results:
- MCPyV DNA prevalence was significantly higher in MPN patients (17.9%) compared to controls (3%) (p = 0.0063, OR = 7.95).
- Positivity for MCPyV DNA was predominantly observed in patients with essential thrombocythemia (ET) (11 out of 14 positive cases).
- MCPyV mRNA was detected, indicating low-level viral transcription in positive samples. Positivity correlated with female sex and myeloproliferative leukemia virus oncogene (MPL) mutations.
Conclusions:
- The findings suggest a potential association between MCPyV and the development of MPNs, especially ET.
- Further research is warranted to elucidate the role of human polyomaviruses in megakaryocytic lineage biology and MPN pathogenesis.
- MCPyV may represent a novel etiological factor or cofactor in a subset of MPN patients.
