T-box-expressed-in-T-cells (T-bet) expression by the tumor cells of hairy-cell leukemia correlates with interferon-gamma production.
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.
Jöhrens
Korinna
K
Consultation and Reference Center for Hematopathology, Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany.
Moos
Verena
V
Schneider
Thomas
T
Anagnostopoulos
Ioannis
I
D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000097:blood* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000098815:T-bet Transcription Factor
D015703:Antigens, CD; D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D016207:Cytokines; D004768:Enterotoxins; D039001:Integrin alpha Chains; D009363:Neoplasm Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C091367:alpha E integrins; C031818:enterotoxin B, staphylococcal; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate