High Subfamily Expression Marks an Improved Overall Survival in Patients With Acute Myeloid Leukemia.

BACKGROUND

Heterogeneous 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 () and TCRδ () subfamilies with diverse structural and functional heterogeneity. Our previous study showed that clonally expanded T cells might benefit the immune response directed against AML. However, the features of the repertoire in AML remain unknown. To fully characterize the features of γδ T cells, we analyzed the distribution and clonality of subfamilies ( is also termed ), the proportions of γδ T cell subsets, and their effects on the overall survival (OS) of patients with AML.

METHODS

In this study, the complementarity-determining region 3 (CDR3) size of subfamilies in γδ T cells of peripheral blood (PB) from AML patients were analyzed by Genescan analysis. Expression levels of 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 gene expression levels, the proportion of Vγ9 Vδ2 T cells, and OS in AML.

RESULTS

We first found that the distribution pattern and clonality of subfamilies were changed. The expression frequencies and gene expression levels of three 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 gene and higher proportion of Vγ9 Vδ2 T cells showed better OS than their counterparts. Furthermore, high expression levels of and proportion of Vγ9 Vδ2 T cells were identified as independent protective factors for complete remission in patients with AML.

CONCLUSIONS

The restriction of usage might be related to the preference of usage of γδ T cells. Higher expression of subfamilies might be associated with better OS in AML. Higher expression and increased Vγ9 Vδ2 T cells subfamilies might indicate a better prognosis in patients with AML.