LMP1+SLAMF1high cells are associated with drug resistance in Epstein-Barr virus-positive Farage cells

Yoon, Hyein; Ko, Young Hyeh

doi:10.18632/oncotarget.15600

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…A copy number gain at 1q23.3 resulting in strong CD150 overexpression is observed in 30.8% of EBV positive DLBCLs case [74]. Moreover, cells with high level of CD150 and LMP1 expression from EBV positive DLBCL derived cell line Farage are characterized by increased resistance to CHOP therapy compared to CD150 low cells [75].…”

Section: Regulation Of Cd150 Expressionmentioning

confidence: 99%

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

Gordiienko

Shlapatska

Kovalevska

et al. 2019

Clinical Immunology

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SLAMF1/CD150 receptor is a founder of signaling lymphocyte activation molecule (SLAM) family of cell-surface receptors. It is widely expressed on cells within hematopoietic system. In hematologic malignancies CD150 cell surface expression is restricted to cutaneous T-cell lymphomas, few types of B-cell non-Hodgkin's lymphoma, near half of cases of chronic lymphocytic leukemia, Hodgkin's lymphoma, and multiple myeloma. Differential expression among various types of hematological malignancies allows considering CD150 as diagnostical and potential prognostic marker. Moreover, CD150 may be a target for antibody-based or measles virus oncolytic therapy. Due to CD150 signaling properties it is involved in regulation of malignant cell fate decision and tumor microenvironment in Hodgkin's lymphoma and chronic lymphocytic leukemia. This review summarizes evidence for the important role of CD150 in pathogenesis of hematologic malignancies.

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Section: Regulation Of Cd150 Expressionmentioning

confidence: 99%

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

Gordiienko

Shlapatska

Kovalevska

et al. 2019

Clinical Immunology

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“…Given the evidence that LMP-1, an oncoprotein encoded by EBV, mimics the constitutively activated CD40 signal in B lymphocyte responses 42 , it is plausible that IL-21 induces EBV-positive DLBCL cell proliferation by a similar mechanism. It has also been reported that cells with high LMP-1 expression are responsible for the poor drug www.nature.com/scientificreports/ response of EBV-positive DLBCL 43 . Combining these results with our previous observations, we hypothesise that the LMP-1 induced in EBV-positive DLBCL cells may be a key factor for proliferation.…”

Section: Discussionmentioning

confidence: 99%

IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma

Wang

Cai

et al. 2020

Sci Rep

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The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBVpositive DLBCL, which has implications for the drug development of DLBCL. Diffuse large B cell lymphoma (DLBCL) accounts for 30% of adult non-Hodgkin's lymphoma (NHL) and is the most common type of malignant lymphoma. Epstein-Barr virus (EBV)-positive DLBCL is a newly defined subgroup of DLBCL that refers to the proliferation of B cell clones carrying EBV 1. The 2008 World Health Organization classification included "Elderly EBV-positive DLBCL" as a temporary entity. However, EBV-positive DLBCL is now increasingly recognised in younger patients, with a broader morphological profile and better survival outcome than originally thought, resulting in the replacement of the name "elderly EBV-positive DLBCL" with "EBV-positive DLBCL" 1. Approximately 10% of all patients with DLBCL present with EBV positivity 2-4. The

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“…Similarly, there was no significant difference in cell cycle distribution among the cell lines ( Fig 2B). We observed overexpression of SLAMF1 at the cell surface of drug resistant Farage cells [14]. We therefore tested whether SLAMF1-deficient Farage cells responded differentially to drugs targeting several pathways.…”

Section: Differential Response To An Akt Inhibitormentioning

confidence: 99%

“…SLAMF1 was known to costimulate proliferation of activated B cells [3]. In a previous study [14], we used SLAMF1 as a surrogate marker for LMP1 and observed that the SLAMF1 high cells grew faster than the SLAMF1 low cells. However, loss of SLAMF1 itself did not obviously alter cell proliferation and cell cycle distribution at the exponential growth phase.…”

Section: Plos Onementioning

confidence: 99%

SLAMF1 contributes to cell survival through the AKT signaling pathway in Farage cells

Yoon

Kim

2020

PLoS ONE

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SLAMF1 is often overexpressed in Epstein Barr virus (EBV)-infected B cell tumors. However, its role in the pathogenesis of EBV-infected B cell tumors remains largely unknown. Here, we generated SLAMF1-deficient EBV+ tumor cells and examined the effect of its deficiency on cell proliferation and cell survival. There were no significant differences in cell proliferation and cell cycle distribution for short periods between the SLAMF1-deficient and wild-type cells. However, the deficient cells were more resistant to an AKT inhibitor (MK-2206). When the both cells were co-cultured and repeatedly exposed to the limitations in nutrition and growth factors, the SLAMF1-deficient cells were gradually decreased. We observed that levels of phospho-AKT were differentially regulated according to the nutritional status between the SLAMF1-deficient and wild-type cells. A decrease in phospho-AKT was observed in SLAMF1-deficient cells as well as an increase in pro-apoptotic Bim just before cell passage, which may have been due to the loss of SLAMF1 under poor growth condition. Overall, SLAMF1 is not a strong survival factor, but it seems to be necessary for cell survival in unfavorable growth condition.

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LMP1+SLAMF1high cells are associated with drug resistance in Epstein-Barr virus-positive Farage cells

Cited by 6 publications

References 45 publications

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma

SLAMF1 contributes to cell survival through the AKT signaling pathway in Farage cells

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