Characteristics of TCRζ, ZAP-70, and FcɛRIγ gene expression in patients with T- and NK/T-cell lymphoma.

Abstract

Abnormal expression of key signaling molecules and defective T-cell function play a crucial role in the pathogenesis of T-cell immunodeficiency in hematological malignancies. To understand the molecular basis of T-cell signaling abnormalities and TCRζ chain deficiencies in T- and NK/T-cell lymphoma, the expression level of the TCRζ, ZAP-70, and FcɛRIγ genes in peripheral blood mononuclear cells from 25 patients with T-cell lymphoma, 16 patients with NK/T-cell lymphoma (NK/T-CL), and 26 healthy individuals was determined. In addition, their relationship with disease stage and TCRζ 3' untranslated region (3'UTR) splice variants was analyzed in this study. The expression level of all three genes was significantly altered with disease progression, and a decreasing trend was found in patients compared with healthy controls. TCRζ and ZAP-70 were significantly positively related in all samples, and a negative relationship between TCRζ and FcɛRIγ was significantly lost in NK/T-CL patients. Moreover, distinct expression patterns were defined for patient groups with different TCRζ 3'UTR isoforms. In conclusion, a lower expression pattern for all three genes may indicate a weaker immune status based on reduced TCRζ and ZAP-70 expression without the complementary effects of FcɛRIγ, while aberrant TCRζ 3'UTR splicing may contribute to T-cell receptor (TCR) signaling regulation in T cells from patients with T- and NK/T-cell lymphoma.