title: Variable expression of CD3-zeta and associated protein tyrosine kinases in lymphocytes from patients with myeloid malignancies.
abstract: In myeloid malignancies, T-cell and NK function has been shown to deteriorate with transformation from pre-leukaemia to advanced disease. Immune dysfunction in solid tumours has been attributed to abnormal signal transduction, possibly through altered expression of intracellular components of the TCR/CD3 complex (e.g. CD3-zeta), receptors on NK cells and their associated protein tyrosine kinases (PTKs; p56lck, p59fyn and ZAP-70). Using a flow cytometric method to detect dual-expression of surface proteins and intracellular components of the TCR/CD3 complex, we have studied 46 patients with myeloid malignancies. CD3-zeta expression was abnormal in 64% of patients, and was more prominent in those with advanced disease. Three patients with reduced CD3-zeta were analysed both pre- and post-treatment, and recovery of CD3-zeta expression was associated with successful remission induction (expression of PTKs was variable and reduced levels were seen all disease stages). The results of this study suggest that loss of signalling proteins is not a result of direct contact of leukaemic cells with lymphocytes per se or the extent of the leukaemia burden, but to a specific property of some myeloid malignancies, which is more frequently acquired with greater malignant transformation.
authors.affiliation: Department of Haematological Medicine, King's College School of Medicine and Dentistry, London.
authors.forename: A G
authors.initials: AG
authors.lastname: Buggins
authors.forename: W J
authors.initials: WJ
authors.lastname: Hirst
authors.forename: A
authors.initials: A
authors.lastname: Pagliuca
authors.forename: G J
authors.initials: GJ
authors.lastname: Mufti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000378:metabolism*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D017452:Receptors, IgG; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)