Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets

• Published in: Scientific reports Vol. 7; no. 1; p. 10188
• Main Authors: Mine, Sohtaro, Hishima, Tsunekazu, Suganuma, Akihiko, Fukumoto, Hitomi, Sato, Yuko, Kataoka, Michiyo, Sekizuka, Tsuyoshi, Kuroda, Makoto, Suzuki, Tadaki, Hasegawa, Hideki, Fukayama, Masashi, Katano, Harutaka
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.08.2017; Nature Publishing Group
• Subjects: 13; 13/106; 45/77; 631/326/596/1553; 692/308/1426; 692/4028/67/1990/291/1621/1915; 692/420/755; 82; 82/51; 82/80; 96/31; 96/95; Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - complications; AIDS; Antibodies, Monoclonal, Humanized; Apoptosis; c-Myc protein; CD20 antigen; CD38 antigen; Cell culture; Cell Culture Techniques - methods; Cell death; Cell differentiation; Cell Line, Tumor; Cell survival; Culture Media - chemistry; Cytokines; Epstein-Barr virus; Genomes; Heavy chains; Humanities and Social Sciences; Humans; Immunoglobulins; Immunophenotyping; Interleukin 6; Interleukin 6 receptors; Interleukin-6 - pharmacology; Lymphoma; Male; Middle Aged; miRNA; multidisciplinary; Myc protein; Plasmablastic Lymphoma - etiology; Plasmablastic Lymphoma - immunology; Plasmablastic Lymphoma - pathology; Science; Science (multidisciplinary); Signal transduction; Starvation; Supplements; TOR protein; Transcription; Translocation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-10684-5

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.