In accordance with cross talk signaling, low level secretion of TGF-β by CML LSCs can support the survival of CML LSCs and leukemia progression through AKT activation, leading to FOXO3A cytosolic localization, mitochondrial dysfunction, and abnormal ROS production [118, 119]. This evidence concerns the gene FOXO3 and chronic myelogenous leukemia, BCR-ABL1 positive.