Analysis of TCR Vgamma and Vdelta Repertoire and Clonality of T Cells in MDS Patients.

Abstract 4833

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. The pathophysiology of these syndromes remains poorly explained. The immune system also seems to contribute to the progressive cytopenias observed in MDS in some cases. We investigated the frequency and the discriminative value of TCR gamma and delta CDR3 clonality using RT-PCR and genescan technique in 40 MDS patients (24 male, 16 female),which included refractory anemia(n=1), refractory anemia with with ringed sideroblasts(n=6), refractory anemia with excess of blasts I (n=16)and II (n=17) respectively. The median age was 60 years (range 15-84).The results showed that 35(87.5%) MDS patients expressed all three TCR Vgamma subfamilies. Four(10%) and one(2.5%) MDS patients expressed two and one TCR Vgamma subfamilies respectively. Clonal expansion of T cells in some Vgamma subfamilies could be identified in 31 patients. The clonal expansion of Vgamma2 subfamily were identified most frequently. All the Vdelta subfamilies were absent in 2 MDS patients. The remaining 38 (95%) MDS cases expressed 0-6 Vdelta subfamilies. Vdelta1 and Vdelta2 were expressed most frequently followed by Vdelta8. While only 3(7.5%) patients expressed Vdelta5 subfamilies. Clonal expansion of Vdelta T cells were found in all MDS patients. The most frequent clonal expansion T cell was Vdelta3. In addition, 12 patients expressed monoclonal T cell Vdelta subfamily. Monoclonal expanded T cells were found in Vdelta3, Vdelta4, Vdelta6, Vdelta7 and Vdelta8 subfamilies. In summary,we found that MDS patients showed TCR Vgamma and delta skew distribution and clonal expansion. The absent of TCR Vdelta subfamily was more evident than TCR Vgamma subfamily. These findings provided further evidence that T cell mediated immune processes were a feature of MDS.