Genomic and functional studies in T-Acute Lymphoblastic Leukemia patients exhibiting clonal T Cell Receptor γ and δ gene rearrangement

T-cell Acute Lymphoblastic Leukemia (T-ALL) is a lymphoid malignancy characterized by clonal proliferation of immature thymocytes arrested at particular stage of differentiation. Earlier studies from our lab have demonstrated that 30% of Indian T-ALL patients exhibited clonal rearrangement of both TCR γ and δ genes. The survival was higher in T-ALL patients showing clonal rearrangements for TCR γ and δ genes. In the present study, we aimed at investigating the gene expression profiles of TCR γδ+ T-ALL patients and correlating it with functional analysis to understand the reasons for increased survival in these patients. Our studies demonstrate differential expression of genes in TCR γδ clonal T-ALL compared to non TCR γδ clonal T-ALL patients. Functional annotation of significantly upregulated genes (p<0.05) in TCR γδ+ T-ALL patients showed involvement in antigen processing and presentation, cell-cell communication, apoptosis, cell adhesion molecules and immune synapse pathways. Expression of eight selected genes (SMAD3, NFkB1, HLA-DQB1, SOCS2, CISH, FASLG, RXRA,and IFNβ1) was validated in TCRαβ+ and TCRγδ+ subgroups of T-ALL patients using quantitative Real-time PCR. Studies focusing on functional aspects of the gene(s) identified from gene expression profile would aid in developing future therapeutic strategies. Agilent one-color experiment,Organism: Human ,Agilent-014850 Whole Human Genome Microarray 4x44K G4112F , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)