Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis

Murakami, Ichiro; Matsushita, Michiko; Iwasaki, Takeshi; Kuwamoto, Satoshi; Kato, Masako; Horie, Yasushi; Hayashi, Kazuhiko; Imamura, Toshihiko; Morimoto, Akira; Imashuku, Shinsaku; Gogusev, Jean; Jaubert, Françis; Takata, Katsuyoshi; Oka, Takashi; Yoshino, Tadashi

doi:10.1016/j.humpath.2013.05.028

Cited by 26 publications

(45 citation statements)

References 35 publications

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“…Our data indicated the possibility that MCPyV is a dermotropic virus. We have previously shown the prevalence of MCPyV in LC in DLA tissues (viral load = 0.001–0.006) and in LC histiocytosis (LCH) lesions (viral load = 0.0001–0.033) [8]. Our data using DLA tissue, in which epidermal LCs with MCPyV migrate into lymph nodes [16,17], suggest that LC is a candidate reservoir of MCPyV in the epidermis.…”

Section: Discussionmentioning

confidence: 58%

“…Therefore, we hypothesized that LC were a reservoir for MCPyV and demonstrated this phenomenon by showing MCPyV-DNA in microdissected LC of dermatopathic lymphadenopathy (DLA) [8]. …”

Section: Resultsmentioning

confidence: 99%

“…MCPyV-positive LCS samples were compared with MCPyV-positive LCH samples [8] in the point of MCPyV viral load in Figure 2 with significant difference (P < 0.01). The presence of MCPyV in LCS lesions suggests three possibilities: a) viral infection as a consequence of LCS development, b) LCS as a bystander, and c) a viral causal agent of LCS.…”

Section: Discussionmentioning

confidence: 99%

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High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues

Murakami

Matsushita

Iwasaki

et al. 2014

Infect Agents Cancer

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BackgroundLangerhans cell (LC) sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytologic features and an LC phenotype. We very recently suggested that LC behaves as a reservoir for common dermotropic Merkel cell polyomavirus (MCPyV) and determined the relationship between LC histiocytosis (LCH), which has an underlining oncogenic capacity, and MCPyV as a trigger for a reactive process rather than a neoplastic process. We propose LC to be a reservoir for MCPyV and hypothesize that some LCS subtypes may be related to the MCPyV agent.FindingsWe examined seven LCS tissues using multiplex quantitative PCR (Q-PCR) and immunohistochemistry with anti MCPyV large-T (LT) antigen antibody. High viral loads of MCPyV DNA sequences (viral load = relative levels of MCPyV) were detected (0.328–0.772 copies/cell (Merkel cell carcinoma (MCC) = 1.0)) using Q-PCR in 43% (3/7) tissues, but LT antigen expression was not observed (0/7).ConclusionsFrequent MCPyV-DNA amplification suggests that LCS in some patients may be related to MCPyV infection. Moreover, the higher viral load of LCS (median, 0.453 copies/cell) than low load of LCH (0.003, median of 12 cases) (P < 0.01) may suggest a virally induced tumorigenic process in some LCS. Although the absence of LT antigen expression may indicate a different role for MCPyV in this pathology, some subtypes of LCS may develop in the background of MCPyV-infected LC. To the best of our knowledge, this is the first report on the relationship between MCPyV and LCS. The recent discovery of MCPyV opened new therapeutic avenues for MCC. These data open novel possibilities for therapeutic interventions against LCS.

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Section: Discussionmentioning

confidence: 58%

“…Therefore, we hypothesized that LC were a reservoir for MCPyV and demonstrated this phenomenon by showing MCPyV-DNA in microdissected LC of dermatopathic lymphadenopathy (DLA) [8]. …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues

Murakami

Matsushita

Iwasaki

et al. 2014

Infect Agents Cancer

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“…La recherche d'agents pathogènes variés a été en règle infructueuse [99,100]. Cependant, très récemment, une équipe a suggéré un rôle potentiel du Merkel cell polyomavirus dans la pathogénie de l'HL [101]. Sur le plan thérapeutique, l'association de corticoïdes inhalés et de bêta-2-sympathomimétiques de longue durée d'action peut améliorer la fonction ventilatoire notamment en cas de réversibilité du trouble ventilatoire obstructif aux EFR.…”

Section: Rôle Du Tabac Dans L'histiocytose Pulmonaireunclassified

Manifestations pulmonaires de l’histiocytose langerhansienne

Obert

Tazi

2015

Revue des Maladies Respiratoires

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Pulmonary Langerhans cell histiocytosis is a rare diffuse cystic interstitial pneumonia of unknown etiology that occurs selectively in young smokers of both genders. The multicenter studies conducted by the reference center have better defined the short and medium terms natural history of the disease and the clinical management of patients. A substantial proportion of patients experience a dramatic decline in their lung function soon after diagnosis. Importantly, smoking cessation is associated with a decreased risk of subsequent deterioration. Cladribine, a purine analogue, chemotherapy may dramatically improve lung function in patients with progressive pulmonary Langerhans cell histiocytosis, but this treatment should be used only in the setting of clinical research. Specific pulmonary hypertension therapies (anti-endothelin receptors, inhibitors of phosphodiesterases) may be used with caution in specialized centres for patients with severe pulmonary hypertension, and seem to be well tolerated. The recent identification of the V600E mutation of the BRAF oncogene in approximately half of the Langerhans cell histiocytosis lesions, including pulmonary granulomas, represents an important step forward in the understanding of the pathogenesis of Langerhans cell histiocytosis. Potentially it opens the way to targeted therapies.

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“…Why does a monocyte-derived DC become an LCH cell? The long-lasting question of a triggering pathogen in LCH has been revitalized by Murakami et al, 29 who recently reported elevated amounts of Merkel cell polyomavirus DNA in the peripheral blood cells of 2 of 3 LCH patients with high-risk organ involvement, but not in the blood cells of 12 of 12 patients with low-risk LCH. Yet with lower viral loads, an elevated number of Merkel cell polyomavirus DNA sequences was detected in 12 LCH tissues compared with controls other than patients with dermatopathic lymphadenopathy.…”

Section: Lch: Inflammatory or Neoplastic?mentioning

confidence: 99%

Blood spotlight on Langerhans cell histiocytosis

Delprat

Aricò

2014

Blood

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Langerhans cell histiocytosis (LCH) is a rare disease affecting people of any age, with widely variable clinical manifestations and different outcomes. The precise chain of events driving lesional granuloma formation has remained elusive for many years. There is evidence for inherited predisposition to and derangement of apoptosis and inflammation in lesional dendritic cells. Recently somatic BRAFV600E mutation in myeloid precursor dendritic cells was associated with the more aggressive form of the disease, although the same mutation in a more differentiated dendritic cell might drive a less aggressive disease. Whether this picture convincingly put LCH in the field of myeloid neoplasm remains to be determined. Altogether, these findings suggest that future therapeutic strategy might incorporate a screening of this genetic mutation for high-risk patients potentially suitable for target therapy.

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Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis

Cited by 26 publications

References 35 publications

High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues

High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues

Manifestations pulmonaires de l’histiocytose langerhansienne

Blood spotlight on Langerhans cell histiocytosis

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