Although the low-level autocrine secretion of transforming growth factor (TGF)-β1 by CML LSC regulates AKT activation and the nuclear localization of forkhead box protein O3 (FOXO3A), thereby maintaining LSC [158], high levels of TGF-β1 released from the extracellular matrix of an actively remodeling BMM have an inhibitory effect on the progression of CML [159] (Figure 2). The gene discussed is FOXO3; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.