Figure 2.

Alternative to BCR-ABL1 signaling network. To evade BCR-ABL1 inhibition, CML cells activate alternative signaling pathways including RAS/MAPK, SRC, JAK/STAT, WNT/b-catenin, hedgehog, and PI3K/AKT. The transduction of oncogenic signals culminates with the activation of multiple downstream signaling pathways that enhance survival, inhibit of apoptosis, and alter cell adhesion and migration. A subset of these pathways and their constituent transcription factors (β-catenin, Gli, STAT5, MYC, FOXO3), serine/threonine-specific kinases (RAS/MAPKs, PI3K/AKT/mTOR), and apoptosis-related proteins (BAD, BCL-2, BCL-XL, survivin) are shown. It is important to note that this is a simplified diagram and that many more associations between BCR-ABL1 and signaling proteins have been reported.