Activation of PI3K/AKT signaling by BCR-ABL1 is an important event in the maintenance of CML LSCs, as it leads to AKT-mediated phosphorylation and cytosolic retention of FOXO transcription factors and therefore decreased transcription of FOXO target genes involved in cell death20,21. This evidence concerns the gene AKT1 and chronic myelogenous leukemia, BCR-ABL1 positive.