Transcriptomics modification consecutive to AS1842856 treatment in primary T lymphocytes

We have observed that the FOXO1 inhibitor AS1842856 induces a significant increase of both the bioenergetics and transcriptional activity of human T cells, together with a significant increase in their size, without any cell division. These modifications are accompanied by a decrease of p27 expression, contrasting with an increase of CDK2 cellular levels and by the phosphorylation of Rb and SAMHD1 proteins. As these changes are known to be characteristic of cells undergoing a G0 to G1 progression. To get an overall view of these changes in T-cell metabolism, we performed gene expression microarray analysis of PBT cultured during 7 days in the presence or not of AS1842856. We conclude that inhibition of FOXO1 by AS1842856 is sufficient to induce a profound reprogramming of human T lymphocytes, regulating their exit from quiescence. Primary T lymphocytes were cultured in the presence of 500 nM of AS1842856 or equivalent amount of DMSO. After 7 days of culture, cells were harvested and RNA was extracted and hybridized on Affymetrix microarrays.