Establishment and characterization of a novel Hodgkin lymphoma cell line, AM-HLH, carrying the Epstein-Barr virus genome integrated into the host chromosome

Hematol Oncol. 2017 Dec;35(4):567-575. doi: 10.1002/hon.2369. Epub 2016 Nov 4.

Abstract

We describe the establishment and characterization of a cell line, AM-HLH, obtained from a patient with Epstein-Barr virus-positive (EBV+ ) nodular sclerosis-type Hodgkin lymphoma (HL). The cells were positive for CD2 and CD30 and negative for CD15. The immunoglobulin heavy- and κ light-chain genes were rearranged. The karyotype was of the triploid range. Southern blotting using the EBV terminal repeat probe detected 3 hybridizing bands that were identical to those of the parental HL material. The cells expressed EBV-encoded RNAs as well as latent genes (EBNA1, EBNA2, LMP1, and LMP2A) and lytic genes (BZLF1 and BALF2). Fluorescence in situ hybridization (FISH) with the cosmid pJB8 clone containing a fragment of EBV DNA as a probe revealed multiple hybridization signals at a marker chromosome. Additional FISH using whole chromosome painting and centromere probes in combination with multicolor FISH determined that multiple EBV copies were clustered within the chromosome 20 materials of the marker chromosome. Culture supernatants of AM-HLH contained IL-10 as measured by the bead-based immunoassay. It is possible that an integrated EBV genome and cellular genes on chromosome 20 were coamplified, leading to the enhanced expression of genes involved in cell growth control. The AM-HLH cell line will be useful to clarify the role of cytokines in the development of EBV+ HL.

Keywords: Epstein-Barr virus; Hodgkin lymphoma cell line; IL-10; chromosomal integration; fluorescence in situ hybridization.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biomarkers
  • Cell Line, Tumor
  • Chromosome Banding
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / virology*
  • Genome, Viral*
  • Herpesvirus 4, Human / genetics*
  • Hodgkin Disease / etiology*
  • Hodgkin Disease / pathology*
  • Host-Pathogen Interactions
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Male
  • Phenotype
  • Virus Integration*

Substances

  • Biomarkers