Elevated IGF1R and abnormal methylated IGF1R in immune thrombocytopenia

To investigate possible role of IGF1R/PI3K/Akt/mTOR signal pathway related genes in the pathogenesis of ITP. Akt/mTOR Total Protein 11-plex Magnetic Bead Kit was used for measurement of related genes of IGF1R/PI3K/Akt/mTOR signal pathway in ITP patients and healthy controls. Genome-wide patterns of DNA methylation and gene expression with IGF1R/PI3K/Akt/mTOR signal pathway were determined in ITP and controls respectively. Elevated protein levels of IGF1R was found in ITP patients compared to healthy controls [Median Fluorescence Intensity (inter-quartile range, IQR), 2551.0 (941.1-4213.0) vs 786.50(276.0-2555.0), P<0.05], the level of p70S6K in ITP patients with active disease was significantly higher [801.0(609.5-1012.0)] than that in healthy controls [652.3(531.8-776.6), P<0.05]. Further study by Genome-wide patterns of DNA methylation showed that differentially methylated regions (DMRs) of IRS1, TSC2 and RPS6KA1 were found in ITP patients. Moreover, methylation variable position of IGF1R was also found in ITP patients. Abnormal elevated expression of IGF1R may play a role through abnormal methylation of IGF1R/PI3K/Akt/mTOR signal pathway in the pathogenesis of ITP.