Abstract
Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(−) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.
Highlights
Plasmablastic lymphoma (PBL) is a rare distinct clinicopathological entity of large B-cell malignant lymphoma, occurring typically in HIV-1 infected or other immunodeficient patients and is generally associated with Epstein– Barr virus (EBV) infection[1, 2]
At the beginning of the primary culture of tumour cells from the patient ascites, cells grew in RPMI 1640 culture medium supplemented with 10% patient ascites, 10% foetal bovine serum (FBS), 10 ng/mL insulin, and 10 ng/mL of transferrin at 37 °C with 5% CO2
The SPIBL-II and III cell lines were established from the pleural effusion of an HIV-positive case of plasmablastic lymphoma
Summary
Plasmablastic lymphoma (PBL) is a rare distinct clinicopathological entity of large B-cell malignant lymphoma, occurring typically in HIV-1 infected or other immunodeficient patients and is generally associated with Epstein– Barr virus (EBV) infection[1, 2]. The incidence of PBL has been estimated as 2–8% of all cases of AIDS-related lymphomas[3, 4]. Integration of EBV in the host chromosome was observed in several cell lines established from EBV-associated lymphoma with persistent infection[8,9,10,11,12,13], there has been no report of an EBV integrated case of PBL. Immortalized cell lines are useful tools to investigate disease pathogenesis and to evaluate the effects of therapeutic agents. To the best of our knowledge, there has been no report describing a well-characterized PBL cell line established from typical PBL cases. We established a PBL cell line from a case of AIDS-associated PBL, and demonstrated its interleukin 6 (IL-6)-dependent growth. The treatment effect of therapeutic agents was investigated
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