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

Sci Rep. 2017 Aug 31;7(1):10188. doi: 10.1038/s41598-017-10684-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Antibodies, Monoclonal, Humanized
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor
  • Culture Media / chemistry
  • Humans
  • Immunophenotyping
  • Interleukin-6 / pharmacology*
  • Male
  • Middle Aged
  • Plasmablastic Lymphoma / etiology
  • Plasmablastic Lymphoma / immunology
  • Plasmablastic Lymphoma / pathology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Culture Media
  • Interleukin-6
  • tocilizumab