The generation of BCR-ABL fusion gene in CML LSCs may have a role in a variety of biological processes, notably cell proliferation, differentiation, and apoptosis by encoding a constitutively activating tyrosine kinase as important mediator of signaling cascades such as RAS/mitogen-activated protein kinase (MAPK), PI3K/Akt/FOXO axis, WNT signaling, and JAK2/STAT3,5 signaling, which are implicated in the maintenance and survival of CML LSCs (Fig. 1) [61, 108]. This evidence concerns the gene JAK2 and chronic myelogenous leukemia, BCR-ABL1 positive.