Individuals with Down syndrome (DS) have a high incidence of immunological alterations with increased susceptibility to bacterial and viral infections and high frequency of different types of hematologic malignancies and autoimmune disorders. In the current study, we profiled the expression pattern of 92 immune-related genes in peripheral blood mononuclear cells (PBMCs) of two different groups, children with DS and control children, to identify differentially expressed genes that might be of pathogenetic importance for the development and phenotype of the immunological alterations observed in individuals with DS. PBMCs samples were obtained from six DS individuals with karyotypically confirmed full trisomy 21 and six healthy control individuals (ages 2–6 years). Gene expression was profiled in duplicate according to the manufacturer's instructions provided by commercially available TaqMan Human Immune Array representing 92 immune function genes and four reference genes on a 96-plex gene card. A set of 17 differentially expressed genes, not located on chromosome 21 (HSA21), involved in immune and inflammatory pathways was identified including 13 genes (BCL2, CCL3, CCR7, CD19, CD28, CD40, CD40LG, CD80, EDN1, IKBKB, IL6, NOS2 and SKI) significantly down-regulated and four genes (BCL2L1, CCR2, CCR5 and IL10) significantly up-regulated in children with DS. These findings highlight a list of candidate genes for further investigation into the molecular mechanism underlying DS pathology and reinforce the secondary effects of the presence of a third copy of HSA21.

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3065 Poster Board III-2 Deregulations of miRNA expression and function in B-cell acute lymphoblastic leukemia (B-ALL) have been associated with specific recurrent citogenetic abnormalities and clinical outcomes. In contrast, there is few data about miRNAs in T-cell acute lymphoblastic leukemia (T-ALL). We have determined the miRNA expression profile of 48 T-ALL patients' blasts and compared with normal mature T cells. We used the Taqman MicroRNA Assay Human Panel to screen 164 known mature miRNA sequences. Normal CD3+ cells were isolated from peripheral blood of four healthy subjects by immunomagnetic labeling. Total RNA was pooled and reverse transcribed with specific looped RT primers, and expression was evaluated by quantitative real-time PCR (RQ-PCR). Reactions were performed in duplicates and samples with a coefficient of variation greater than 5% were excluded. Furthermore, we considered as differentially expressed those miRNAs with fold change values higher than 10 or lower than 0.1. With this strategy we identified four miRNAs that were hyper-expressed (miR-181a, miR-181b, miR-213 and miR-29b) and three hypo-expressed (miR-150, miR-95, miR-338) in the leukemic pool. In order to confirm our findings, we then performed the analysis of miR-181a, miR-181b and miR-29b expression on 52 individual samples (48 T-ALL and 4 normal T cell samples) using RQ-PCR. Forty-five (93.7%) and 46 (95.8%) of the T-ALL samples presented expression levels of miR-29b and of miRs 181a/181b higher than the maximum detected in the normal samples. The analysis of the predicted targets for these three miRNAs was performed using miRNApath. MAPK signaling was the pathway with the highest number of target genes with 60 genes, of which MAP4K4, FOS, RAP1B, AKT3 and NLK were commonly targeted by all three miRNAs. As deregulation of the MAPK pathway in T-ALL has been previously described, we hypothesized that the hyper-expression of miR-29b, miR-181a and miR181b may be associated with this aberrant MAPK signaling. Disclosures No relevant conflicts of interest to declare.

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