As a result, the overactivation of the downstream signal transduction pathways (PI3K/AKT, Ras/MEK/ERK, JAK2/STAT5) restrain the expression of transcription factors involved in myeloid differentiation, such as PU1 and C/EBPα, and upregulate the expression of many other genes that support AML cell proliferation.134 FLT3-ITD also suppresses the activity of the transcription factor FOXO3a, which is a positive regulator of apoptosis by instigating TRAIL expression.146 Through the consequential activation of AKT, FOXO3a receives an inhibitory phosphorylation. Here, AKT1 is linked to acute myeloid leukemia.