Comparison of the Distribution and Clonal Expansion Features of the T-Cell γδ Repertoire in Myelodysplastic Syndrome-RAEB and RAEB with Progression to AML

Abstract

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell diseases. Approximately 30% of patients with MDS will develop acute myeloid leukemia (AML). Immune dysregulation may contribute to MDS initiation and progression. The altered expression and clonal expansion of the Vβ repertoire were observed in patients with MDS. To further examine the characteristic features of γδ(+)T cells in MDS, we investigated the distribution pattern and clonal expansion capacity of the T-cell receptor (TCR) Vγ and Vδ repertoire in patients with refractory anemia with excess of blasts (RAEB) and compared the difference between groups of patients with RAEB and RAEB-AML. Thirty-one patients with newly diagnosed MDS-RAEB were enrolled, and 9 of the 31 patients with RAEB developed AML (RAEB-AML). The TCR Vγ subfamily expression frequencies were similar in the RAEB and RAEB-AML patient groups. The number of the TCR Vδ subfamilies expressed in the RAEB group was higher than that in the RAEB-AML group. In most cases, a significantly higher Vδ4 subfamily expression frequency (63.64%, 14/22) could be detected in the RAEB group, whereas only 11.11% (1/9) was found in the RAEB-AML group (p=0.0079). At least one clonally expanded TCR Vδ subfamily member was detected in all cases in both groups. Vδ3 was the most frequent clonally expanded T cell subfamily member found in the RAEB and RAEB-AML group, while the most frequent clonally expanded T cell subfamily member in the RAEB-AML group was Vδ8 (87.5%, 7/8), which was significantly higher than that in the RAEB group (42.86%, 9/21; p=0.0307). In conclusion, the TCR Vδ subfamily expression pattern exhibited a marked restriction in patients with RAEB-AML. The lower Vδ4 frequency and higher clonally expanded Vδ8 T cell alterations were the characteristic features found in RAEB-AML. These results provide new data regarding the immunodeficiency and immune reactive characteristics of patients with RAEB and RAEB-AML.