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