Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood

Ohga, Shouichi; Ishimura, Masataka; Yoshimoto, Goichi; Miyamoto, Toshihiro; Takada, Hidetoshi; Tanaka, Tamami; Ohshima, Koichi; Ogawa, Yoshiyasu; Imadome, Ken Ichi; Abe, Yasunobu; Akashi, Koichi; Hara, Toshiro

doi:10.1016/j.jcv.2011.01.014

Cited by 28 publications

(11 citation statements)

References 32 publications

(29 reference statements)

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“…Biphasic expansion of EBV-infected lymphocytes has been demonstrated in some patients with SCAEBV. (34)(35)(36)(37) A recent study using an immuno-FISH assay, which is similar to the FISH assay used in the present study and can characterize EBV-infected cell phenotypes, revealed that not only T/NK cells, but also monocytes were infected with EBV in patients with EBV-associated LPD. (38) There are several possible explanations as to why multiple cell lineages were infected with EBV.…”

Section: Discussionsupporting

confidence: 59%

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Application of flow cytometric in situ hybridization assay to Epstein–Barr virus‐associated T/natural killer cell lymphoproliferative diseases

et al. 2012

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Epstein–Barr virus (EBV) infects various types of lymphocytes and is associated with not only B cell‐origin lymphoma, but also T or natural killer cell lymphoproliferative diseases (T/NK LPD). Recently, we established a novel assay to identify EBV‐infected cells using FISH. Using this assay, dual staining with antibodies to both surface antigens and an EBV‐encoded small RNA (EBER) probe can be performed. In the present study, we applied this recently developed FISH assay to EBV‐associated T/NK LPD to confirm its diagnostic utility. Using FISH, we prospectively analyzed peripheral blood from patients with suspected EBV‐associated T/NK LPD. The results were compared with those obtained using immunobead sorting followed by quantitative PCR. In all, 26 patients were included study. Using FISH, 0.15–67.0% of peripheral blood lymphocytes were found to be positive for EBER. Dual staining was used to determine EBER‐positive cell phenotypes in 23 of 26 subjects (88.5%). In five of seven patients with hydroa vacciniforme‐like lymphoma (an EBV‐positive cutaneous T cell lymphoma), EBER‐positive cells were identified as CD3+CD4−CD8− TCRγδ+ T cells. Furthermore, in a 25‐year‐old male patient with systemic EBV‐positive T cell LPD, two lymphocyte lineages were positive for EBER: CD4+CD8− and CD4−CD8+T cells. Thus, we confirmed that our newly developed assay is useful for quantifying and characterizing EBV‐infected lymphocytes in EBV‐associated T/NK LPD and that it can be used not only to complement the pathological diagnosis, but also to clarify the pathogenesis and to expand the spectrum of EBV‐associated diseases. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02305.x, 2012)

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Section: Discussionsupporting

confidence: 59%

“…Second, EBV may infect hematopoietic stem cells that differentiate to multiple cell lineages. Third, EBV-infected lymphocytes may be capable of differentiation, as suggested recently by Ohga et al (37) Further studies are necessary to clarify the mechanism by which EBV infects multiple lineages.…”

Section: Discussionmentioning

confidence: 83%

Application of flow cytometric in situ hybridization assay to Epstein–Barr virus‐associated T/natural killer cell lymphoproliferative diseases

et al. 2012

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“…The clonal chromosomal abnormalities associated with poor prognosis were highlighted in many other studies [6,7,9,[12][13][14][15][16]. In our patient, a complex karyotype was revealed by chromosomal analysis, and the disease rapidly took a fatal course.…”

Section: Case Reportsupporting

confidence: 56%

Systemic Epstein-Barr Virus-Positive T-cell Lymphoproliferative Disease of Childhood Presenting as Hemophagocytic Lymphohistiocytosis with Chromosomal Abnormalities

Yang¹,

Chung²,

Mun³

et al. 2014

J Lab Med Qual Assur

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“…This latter point is relevant to cases of CAEBV and HLH where both cell types may carry EBV in the same patient. Indeed, one recent study on childhood T/NK lymphoproliferations indicated that in some cases the same monoclonal EBV might be present in different cell populations, although no evidence of infection of CD34 + stem cells was found [206]. …”

Section: Unanswered Questions In Ebv-associated Nk and T Lymphoprolifmentioning

confidence: 99%

Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations

2011

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Epstein-Barr virus (EBV) is a highly successful herpesvirus, colonizing more than 90% of the adult human population worldwide, although it is also associated with various malignant diseases. Primary infection is usually clinically silent, and subsequent establishment of latency in the memory B lymphocyte compartment allows persistence of the virus in the infected host for life. EBV is so markedly B-lymphotropic when exposed to human lymphocytes in vitro that the association of EBV with rare but distinct types of T and NK cell lymphoproliferations was quite unexpected. Whilst relatively rare, these EBV-associated T and NK lymphoproliferations can be therapeutically challenging and prognosis for the majority of patients is dismal. In this review, we summarize the current knowledge on the role of EBV in the pathogenesis of these tumours, and the implications for treatment.

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Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood

Cited by 28 publications

References 32 publications

Application of flow cytometric in situ hybridization assay to Epstein–Barr virus‐associated T/natural killer cell lymphoproliferative diseases

Application of flow cytometric in situ hybridization assay to Epstein–Barr virus‐associated T/natural killer cell lymphoproliferative diseases

Systemic Epstein-Barr Virus-Positive T-cell Lymphoproliferative Disease of Childhood Presenting as Hemophagocytic Lymphohistiocytosis with Chromosomal Abnormalities

Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations

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