Abstract
BackgroundHeterogeneous T cells in acute myeloid leukemia (AML) have the combinatorial variety generated by different T cell receptors (TCRs). γδ T cells are a distinct subgroup of T cells containing TCRγ (TRGV) and TCRδ (TRDV) subfamilies with diverse structural and functional heterogeneity. Our previous study showed that clonally expanded TRDV T cells might benefit the immune response directed against AML. However, the features of the TRGV repertoire in AML remain unknown. To fully characterize the features of γδ T cells, we analyzed the distribution and clonality of TRGV I-III subfamilies (TRGV II is also termed TRVG 9), the proportions of γδ T cell subsets, and their effects on the overall survival (OS) of patients with AML.MethodsIn this study, the complementarity-determining region 3 (CDR3) size of TRGV subfamilies in γδ T cells of peripheral blood (PB) from de novo AML patients were analyzed by Genescan analysis. Expression levels of TRGV subfamilies were performed by real-time quantitative PCR. The proportions of total γδ T cells and their Vγ9+ Vδ2+ T cells subsets were detected by multicolor flow cytometry assay. We further compared the correlation among the TRGV gene expression levels, the proportion of Vγ9+ Vδ2+ T cells, and OS in AML.ResultsWe first found that the distribution pattern and clonality of TRGV subfamilies were changed. The expression frequencies and gene expression levels of three TRGV subfamilies in AML samples were significantly lower than those in healthy individuals (HIs). Compared with HIs, the proportions of total γδ T cells and Vγ9+ Vδ2+ T cells were also significantly decreased in patients with AML. In addition, patients with AML who had higher expression levels of the TRGV gene and higher proportion of Vγ9+ Vδ2+ T cells showed better OS than their counterparts. Furthermore, high expression levels of TRGV 9 and proportion of Vγ9+ Vδ2+ T cells were identified as independent protective factors for complete remission in patients with AML.ConclusionsThe restriction of TRGV usage might be related to the preference of usage of γδ T cells. Higher expression of TRGV subfamilies might be associated with better OS in AML. Higher TRGV 9 expression and increased Vγ9+ Vδ2+ T cells subfamilies might indicate a better prognosis in patients with AML.
Highlights
Acute myeloid leukemia (AML) is a malignant clonal disease originating from hematopoietic stem cells and characterized by genetic and clinical heterogeneity and high mortality [1]
Genes encode for the variable domains of TRG (g chain) and TRD (d chain), which are assembled by somatic recombination from variable (V), diversity (D, only for TRD), and joining (J) segments and compose three hypervariable or complementarity-determining regions (CDR1, CDR2, and CDR3) that occur during T cell differentiation [5, 6]
The CDR3 region of three TRG gene contains several different functional variable (TRGV) subfamily genes was analyzed by Genescan analysis in gd T cells from 30 patients with de novo AML and 10 healthy individuals (HIs) to assess the spectral pattern visually
Summary
Acute myeloid leukemia (AML) is a malignant clonal disease originating from hematopoietic stem cells and characterized by genetic and clinical heterogeneity and high mortality [1]. The analysis of TRGV repertoire was acquired in three TRGV subfamilies in the present study Nowadays, according to their TRD (TCRd) chain usage, human gd T cells are mainly divided into 2 major subsets including Vd1 and Vd2 in peripheral blood (PB). Heterogeneous T cells in acute myeloid leukemia (AML) have the combinatorial variety generated by different T cell receptors (TCRs). Gd T cells are a distinct subgroup of T cells containing TCRg (TRGV) and TCRd (TRDV) subfamilies with diverse structural and functional heterogeneity. To fully characterize the features of gd T cells, we analyzed the distribution and clonality of TRGV I-III subfamilies (TRGV II is termed TRVG 9), the proportions of gd T cell subsets, and their effects on the overall survival (OS) of patients with AML
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