T-box-expressed-in-T-cells (T-bet) expression by the tumor cells of hairy-cell leukemia correlates with interferon-gamma production

Leuk Lymphoma. 2009 Oct;50(10):1687-92. doi: 10.1080/10428190903161042.

Abstract

Hairy cell leukemia (HCL) is an uncommon B-cell malignancy with unknown pathogenesis. In an earlier study, we demonstrated that HCL cells highly express the transcription factor T-box-expressed-in-T-cells (T-bet). T-bet is the master regulator of the T-helper (Th)1 cell response regulating interferon gamma (IFN-gamma) production and also plays a central role in the T-cell independent Th1-like B-cell response. Here, we demonstrate by fluorescence activated cell sorting (FACS) analysis that neoplastic cells from the peripheral blood of five patients with HCL showed an enhanced expression of IFN-gamma after stimulation. Additionally, a comparison with 55 healthy individuals revealed a significant elevation of IFN-gamma in the sera of patients with HCL. Based on our recent findings that a non-neoplastic B-cell subset, the monocytoid B-cells, are T-bet positive and produce IFN-gamma, we propose that monocytoid and hairy B-cells have a similar function and that the T-bet-IFN-gamma axis is involved in the pathogenesis of HCL.

MeSH terms

  • Antigens, CD / analysis
  • Antigens, CD19 / analysis
  • Antigens, Neoplasm / analysis
  • B-Lymphocyte Subsets / metabolism*
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Cytokines / metabolism
  • Enterotoxins / pharmacology
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Immunophenotyping
  • Integrin alpha Chains / analysis
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Ionomycin / pharmacology
  • Leukemia, Hairy Cell / blood*
  • Leukemia, Hairy Cell / etiology
  • Leukemia, Hairy Cell / genetics
  • Leukemia, Hairy Cell / pathology
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology*
  • T-Box Domain Proteins / physiology*
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, CD
  • Antigens, CD19
  • Antigens, Neoplasm
  • Cytokines
  • Enterotoxins
  • Integrin alpha Chains
  • Neoplasm Proteins
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • alpha E integrins
  • enterotoxin B, staphylococcal
  • Ionomycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate