The MEC1 and MEC2 Lines Represent Two CLL Subclones in Different Stages of Progression Towards Prolymphocytic Leukemia

PLoS One. 2014 Aug 27;9(8):e106008. doi: 10.1371/journal.pone.0106008. eCollection 2014.

Abstract

The EBV carrying lines MEC1 and MEC2 were established earlier from explants of blood derived cells of a chronic lymphocytic leukemia (CLL) patient at different stages of progression to prolymphocytoid transformation (PLL). This pair of lines is unique in several respects. Their common clonal origin was proven by the rearrangement of the immunoglobulin genes. The cells were driven to proliferation in vitro by the same indigenous EBV strain. They are phenotypically different and represent subsequent subclones emerging in the CLL population. Furthermore they reflect the clinical progression of the disease. We emphasize that the support for the expression of the EBV encoded growth program is an important differentiation marker of the CLL cells of origin that was shared by the two subclones. It can be surmised that proliferation of EBV carrying cells in vitro, but not in vivo, reflects the efficient surveillance that functions even in the severe leukemic condition. The MEC1 line arose before the aggressive clinical stage from an EBV carrying cell within the subclone that was in the early prolymphocytic transformation stage while the MEC2 line originated one year later, from the subsequent subclone with overt PLL characteristics. At this time the disease was disseminated and the blood lymphocyte count was considerably elevated. The EBV induced proliferation of the MEC cells belonging to the subclones with markers of PLL agrees with earlier reports in which cells of PLL disease were infected in vitro and immortalized to LCL. They prove also that the expression of EBV encoded set of proteins can be determined at the event of infection. This pair of lines is particularly important as they provide in vitro cells that represent the subclonal evolution of the CLL disease. Furthermore, the phenotype of the MEC1 cells shares several characteristics of ex vivo CLL cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • B-Lymphocytes / virology
  • Biomarkers / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Clonal Evolution / immunology
  • Clone Cells / immunology
  • Clone Cells / pathology
  • Clone Cells / virology
  • Disease Progression
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Epstein-Barr Virus Nuclear Antigens / metabolism
  • Gene Expression
  • Herpesvirus 4, Human / physiology
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / virology
  • Leukemia, Prolymphocytic / immunology
  • Leukemia, Prolymphocytic / pathology*
  • Leukemia, Prolymphocytic / virology
  • Lymphocyte Count
  • Time Factors
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Biomarkers
  • EBNA-2 protein, Human herpesvirus 4
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • Viral Matrix Proteins
  • Viral Proteins

Grant support

This work was supported by the Swedish Cancer Society and by the Cancer Research Institute (New York, NY)/Concern Foundation (Los Angeles, CA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.