Measles virus: evidence of an association with Hodgkin's disease

Benharroch, Daniel; Shemer‐Avni, Yonat; Yy, Myint; Levy, Amalia; E, Mejirovsky; Suprun, Irena; Shendler, Yaakov; Prinsloo, Isebrand; Ariad, Samuel; Rager-Zisman, Bracha; Sacks, Martin; Gopas, Jacob

doi:10.1038/sj.bjc.6601900

Cited by 36 publications

(62 citation statements)

References 39 publications

(33 reference statements)

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“…Few subjects reported measles over the age of 10 years and subjects infected over the age of 4 years appeared to have reduced risk of young adult cHL. These data, therefore, do not support the speculation 21 that late exposure to MV, which can occur in unvaccinated patients and in vaccinated young adult patients with waning immunity, 39 is associated with an increased risk of young adult HL. When we considered age at MV infection, Ôall casesÕ and EBV2ve cHL cases in the young adult age group were significantly more likely to report measles below the age of 5 years when compared to those who reported measles at older ages.…”

Section: Discussioncontrasting

confidence: 59%

“…20,21 Although cautious about attributing a causal role to the virus, they suggested that the time was ripe for an international effort to verify (or refute) their findings. 20 We therefore examined this association using both epidemiological and laboratory-based methods.…”

Section: Discussionmentioning

confidence: 99%

“…Nested PCR reactions for the MV haemagglutinin (HA) 38 and NP genes were performed using the primers shown in Table III; these primers are identical to those used by Benharroch et al 21 In and 100 ng of cDNA template were used in a total reaction volume of 50 ll. Amplification was performed using a GeneAmp PCR System 9700 (Applied Biosystems, Warrington, UK) using the following thermal cycling conditions: 94°C for 2 min followed by 35 cycles (HA assay) or 40 cycles (NP assay) of 94°C for 30 s; 46°C (HA assay) or 55°C (NP assay) for 1 min; 72°C for 30 s and a final extension at 72°C for 5 min.…”

Section: Conventional Pcrmentioning

confidence: 99%

“…20,21 Prompted by epidemiological findings, they used immunohistochemistry (IHC), RT-PCR and in situ hybridisation to look for evidence of MV in a cohort of 154 HL patients. A panel of commercial and experimental antibodies was used in the IHC studies and cases scored as positive if HRS cells reacted with more than 1 antibody.…”

Section: 10mentioning

confidence: 99%

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Measles virus and classical Hodgkin lymphoma: No evidence for a direct association

Wilson

Freeland

Gallagher

et al. 2007

Intl Journal of Cancer

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A proportion of Hodgkin lymphoma (HL) cases are causally associated with the Epstein-Barr virus (EBV) but the aetiology of the remaining cases remains obscure. Over the last 3 decades several studies have found an association between HL and measles virus (MV) including a recent cohort study describing the detection of MV antigens in Hodgkin and Reed-Sternberg cells, the tumour cells in HL. In the present study we looked at the relationship between history of MV infection and risk of developing HL in a population-based, case/control study of HL. In addition we used immunohistochemistry and RT-PCR to look for direct evidence of MV in HL biopsies. There was no significant difference in the proportion of cases reporting previous measles compared to controls in the entire data set or when young adults were considered separately. Using a robust immunohistochemical assay for MV infection, we failed to find evidence of MV in biopsies from 97 cases of HL and RT-PCR studies similarly gave negative results. This study therefore provides no evidence that MV is directly involved in the development of HL. However, when age at first reported MV infection was investigated, significant differences emerged with children infected before school-age having higher risk, especially of EBV2ve HL, when compared with children infected at older ages; the interpretation of these latter results is unclear. ' 2007 Wiley-Liss, Inc.Key words: Hodgkin lymphoma; measles virus; PCR; epidemiology The term Hodgkin lymphoma (HL) encompasses 2 entities, nodular lymphocyte predominant HL and classical HL (cHL), which are now recognised as distinct disease processes.1 The pathology and epidemiology of cHL, which accounts for almost 95% of cases, also suggest that this is a heterogeneous entity that is likely to have more than one aetiology.2 Histologically, cHL is divided into 4 subtypes on the basis of the appearance of the rare tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, and the composition of the more plentiful background infiltrate.3 The most common subtypes are nodular sclerosis (NSHL) and mixed cellularity (MCHL).3 cHL generally shows a bimodal age-specific incidence curve but there is marked geographical variation in the shape of the curve and the age at which the incidence peaks occur. 4,5 It is the most common lymphoma in young adults in the Western world and the most common childhood malignancy in some developing countries.6,7 Epstein-Barr virus (EBV) is present in the HRS cells in a proportion of cHL cases and is believed to contribute to disease causation.8 EBV-associated cases (EBV1ve cHL) are not evenly distributed across all patient subgroups; cases of the MCHL subtype are more likely to be EBV-associated than NSHL cases, as are cases diagnosed in early childhood (<10 years) and older adulthood (>50 years).2 Consistent with this, a higher proportion of cases in developing countries are EBV-associated compared to developed countries, in which around 33% of cHL cases are EBV-positive. 9,10An increased risk of developing young...

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Conventional Pcrmentioning

confidence: 99%

Section: 10mentioning

confidence: 99%

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Measles virus and classical Hodgkin lymphoma: No evidence for a direct association

Wilson

Freeland

Gallagher

et al. 2007

Intl Journal of Cancer

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“…21 There are also recent indications that measles virus and TT viruses may be involved in HL pathogenesis, but this needs further confirmation. 22,23 Furthermore, over the last years several aberrantly expressed proteins and inappropriately activated signalling pathways have been identified, which are important for HRS cell phenotype, survival and proliferation, but for which the causing genetic alterations are still unknown. The following discussion focuses on recent advances in 4 central fields of classical HL research, namely the aberrant activation of multiple signalling pathways in HRS cells, antiapoptotic mechanisms important for HRS cell survival, the pathogenesis of composite lymphomas and new insights into the role of EBV in HRS-cell pathogenesis and the survival of crippled GC B cells.…”

mentioning

confidence: 99%

Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma

Bräuninger

Schmitz

Bechtel

et al. 2005

Intl Journal of Cancer

172

116

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Hodgkin's and Reed/Sternberg (HRS) cells, the tumour cells in classical Hodgkin's lymphoma (HL), represent transformed B cells in nearly all cases. The detection of destructive somatic mutations in the rearranged immunoglobulin (Ig) genes of HRS cells in classical HL indicated that they originate from preapoptotic germinal centre (GC) B cells that lost the capacity to express a highaffinity B-cell receptor (BCR). Several aberrantly activated signalling pathways and transcription factors have been identified that contribute to the rescue of HRS cells from apoptosis. Among the deregulated signalling pathways, activation of multiple receptor tyrosine kinases in HRS cells appears to be a specific feature of HL. In about 40% of cases of classical HL the HRS cells are infected by Epstein-Barr virus (EBV), indicating an important role of EBV in HL pathogenesis. Interestingly, nearly all cases of HL with destructive Ig gene mutations eliminating BCR expression (e.g. nonsense mutations) are EBV-positive, suggesting that EBV-encoded genes have a particular function to prevent apoptosis of HRS-cell precursors that acquired such crippling mutations. This idea is further supported by the recent demonstration that isolated human GC B cells harbouring crippled Ig genes can be rescued by EBV from cell death, giving rise to lymphoblastoid cell lines. The molecular analysis of composite Hodgkin's and nonHodgkin's lymphomas indicated that many cases develop from a common GC B-cell precursor in a multistep transformation process with both shared and distinct oncogenic events. 2-6 Nearly all cases of classical and lymphocyte-predominance HL carry somatically mutated V genes, suggesting an origin from (post) germinal centre (GC) B cells, as somatic hypermutation of Ig V genes specifically takes place in GC B cells.7 In lymphocyte-predominance HL, the detection of intraclonal V gene diversity and several phenotypic features suggest an origin of the L&H cells from mutating and selected GC B cells. 2,4,5 In classical HL, crippling mutations that destroyed the coding capacity of originally functional rearrangements were detected in about a quarter of cases.3,8 Such obviously crippling mutations happen in mutating GC B cells, but represent only a small fraction of all disadvantagous mutations that normally result in apoptosis of the respective GC B cells. In the GC, there is a stringent selection for B cells acquiring affinity-increasing mutations, so also many GC B cells that still express a B-cell receptor (BCR) but which fails to bind to the cognate antigen with improved affinity will undergo apoptosis.9,10 Thus, we speculated that the vast majority of HRS cells in classical HL are derived from preapoptotic GC B cells. 3 In rare cases (about 2%) HRS cells originate from T cells. 11,12 Although HRS cells are usually transformed B cells, global gene expression analysis of HRS cell lines using microarrays revealed that the HRS cells have lost the expression of most B-cell markers to an extent that is unique among B-cell lymphomas. 13 As t...

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Lymphomas

and¹,

Pinkerton²

2006

Pediatric Hematology

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Measles virus: evidence of an association with Hodgkin's disease

Cited by 36 publications

References 39 publications

Measles virus and classical Hodgkin lymphoma: No evidence for a direct association

Measles virus and classical Hodgkin lymphoma: No evidence for a direct association

Molecular biology of Hodgkin's and Reed/Sternberg cells in Hodgkin's lymphoma

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